Long-Term Outcomes and Prognostic Factors in Periampullary Carcinoma

Abstract

Purpose

The aim of the study was to analyze the long-term survival and the various prognostic factors that influence overall survival in patients undergoing pancreaticoduodenectomy (PD) with non-pancreatic periampullary carcinomas.

Methods

A retrospective analysis of consecutive patients diagnosed with non-pancreatic periampullary carcinomas who underwent PD at a tertiary cancer center was performed. Univariate analysis of various prognostic factors influencing the disease-free survival (DFS) was performed using log-rank test. Factors identified to be significant in univariate analysis were included in the multivariate analysis, which was performed using the Cox proportional hazard model. The survival estimates were calculated by life-table method. Statistical significance was considered when p value was <0.05. The SPSS v16.0.1 software was used for statistical analysis.

Results

Between 1995 and 2010, 78 patients underwent PD with or without (Whipple's operation) pylorus preservation for non-pancreatic periampullary adenocarcinomas. Of these, eight patients received adjuvant chemotherapy. The most common subsite was ampulla (60 patients), followed by the second part duodenum (11 patients), and distal common bile duct (7 patients). The median duration of follow-up of all patients in this study was 50 months. The recurrence rate was 39.7 %. The 5-year disease-free survival and overall survival was 57 %. Patients without nodal metastasis had a non-significant trend towards better 5-year disease-free survival when compared to those with nodal metastasis (64 vs 45 %, p = 0.11). On multivariate analysis, it was found that male gender (p = 0.05) and presence of lymphovascular invasion (p = 0.04) predicted a significantly poor 5-year disease-free survival.

Conclusion

Periampullary carcinomas have a favorable prognosis after surgery. Male gender and presence of lymphovascular invasion are independent prognostic factors in patients diagnosed with non-pancreatic periampullary carcinomas who underwent PD in this study.

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

Cancer of the vulva in Burkina Faso: a hospital-based case series

Abstract

Background

Vulvar cancer is a rare gynaecological cancer. In Burkina Faso, the diagnosis of vulvar cancers is delayed and the prognosis is poor. However, no specific study on vulvar cancers has been conducted at the moment. This work aimed to study the characteristics of these cancers.

Methods

This is a prospective study on histologically confirmed primary cancers of the vulva diagnosed between 1st January 2013 and 30th June 2015. The demographic and clinical aspects were studied at the Yalgado Ouedraogo University Hospital of Ouagadougou (CHU-YO).

Results

We noticed 21 cases of vulvar cancers within 30 months, ranking it as the 4th most common gynaecological cancer. The average age of the patients was 55 years (standard deviation +/− 6.3) and the median age was 57 years. Scars resulting from female circumcision, menopause (n = 20) and HIV infection were noticed in 19 cases and 6 cases respectively. The average time from first symptoms to first consultation was 29 months. Pain and ulceration were the main reasons for consultation. The clinical picture was chiefly an ulcero-granulating tumour. There was squamous cell carcinoma in 20 cases and basal carcinoma in 1 case. Fifteen patients were at stage III or IV, where of three patients had metastatic disease. We noticed vitiligo in 9 vulvar cancer cases.

Conclusion

The cancer of the vulva is rare. Women are of menopausal age, are mostly circumcised and HIV-infection is common. A majority of patients sought consultation at advanced stage of disease, and diagnosis was belatedly made. Pain and ulceration were the main reasons for consultation. The sensitization of the population, education for self- examination would allow earlier diagnosis.

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

Assessment of Fever Advisory Cards (FACs) as an Initiative to Improve Febrile Neutropenia Management in a Regional Cancer Center Emergency Department [Quality in Action]

Purpose:

We aimed to improve the time to antibiotics (TTA) for patients treated with chemotherapy who present to the emergency department (ED) with febrile neutropenia (FN) by using standardized fever advisory cards (FACs).

Methods:

Patients treated with chemotherapy who visited the ED at the Peel Regional Cancer Center in Ontario, Canada, with suspected FN were identified, before (April 2012 to March 2013) and after (October 2013 to March 2014) FAC implementation. The primary outcome of interest was TTA. Additional process measures included Canadian Triage and Acuity Scale score, time to physician assessment, and FAC compliance. Outcomes were analyzed with descriptive statistics and control charts to determine whether the change in primary measures were within statistical control over time.

Results:

Between the pre-FAC cohort (n = 239) and post-FAC cohort (n = 69), TTA did not change significantly post-FACs (195 v 244 min, P = .09), with monthly averages demonstrating normal variation by statistical process control methodology. The introduction of FACs increased the percentage of patients with correctly assigned Canadian Triage and Acuity Scale scores (87% v 100%) but did not affect time to physician assessment. Compliance with FACs among patients was not ideal, with only 62.5% using them as intended.

Conclusion:

The distribution of FACs was associated with an improved incidence of correct FN triaging but did not demonstrate a meaningful improvement in the quality of FN management. This may be explained by FAC use among patients not being ideal. Next steps in the continued effort toward high-quality FN care include redesign of FACs, reinforcement of provider and patient education, and ED outreach.

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

Galectin-4 promotes prostate cancer metastasis

Metastatic prostate cancer (PCa) continues to pose a difficult therapeutic challenge. PCa progression is associated with aberrant O-glycosylation of cancer cell surface receptors, but the functional impact of such events are uncertain. Here we report spontaneous metastasis of human PCa xenografts which express high levels of galectin-4 along with genetic signatures of EGFR-HER2 signaling and O-glycosylation. Galectin-4 expression in clinical specimens of PCa correlated with poor patient survival. Galectin-4 binding to multiple receptor tyrosine kinases stimulated their autophosphorylation, activated expression of pERK, pAkt, fibronectin and Twist1, and lowered expression of E-cadherin, thereby faciliating epithelial-mesenchyme transition, invasion and metastasis. In vivo investigations established that galectin-4 expression enabled PCa cells to repopulate tumors in orthotopic and heterotopic tissues. Notably, these effects of galectin-4 relied upon O-glycosylation mediated by C1GALT1, a galactosyltransferase implicated in other cancers. Parallel changes in galectin-4 and O-glycosylation triggered aberrant receptor signaling and more aggressive invasive character in PCa cells, which through better survival in the circulation also contributed to the bulk cell progeny of distal tumors. Our findings establish galectin-4 and C1GALT1-mediated glycosylation in a signaling axis that is activated during CaP progression, with implications for therapeutic targeting of advanced metastatic disease.

from Cancer via ola Kala on Inoreader http://ift.tt/2ah01O5
via IFTTT

mechanism-of-action of PP2A A{alpha} subunit cancer mutants

Somatic missense mutations in the Ser/Thr protein phosphatase 2A (PP2A) Aα scaffold subunit gene PPP2R1A are among the few genomic alterations that occur frequently in serous endometrial carcinoma (EC) and carcinosarcoma, two clinically aggressive subtypes of uterine cancer with few therapeutic options. Previous studies reported that cancer-associated Aα mutants exhibit defects in binding to other PP2A subunits and contribute to cancer development by a mechanism of haploinsufficiency. Here we report on the functional significance of the most recurrent PPP2R1A mutations in human EC which cluster in Aα HEAT repeats 5 and 7. Beyond predicted loss-of-function effects on the formation of a subset of PP2A holoenzymes, we discovered that Aα mutants behave in a dominant-negative manner due to gain-of-function interactions with the PP2A inhibitor TIPRL1. Dominant-negative Aα mutants retain binding to specific subunits of the B56/B' family and form substrate trapping complexes with impaired phosphatase activity via increased recruitment of TIPRL1. Accordingly, overexpression of the Aα mutants in EC cells harboring wildtype PPP2R1A increased anchorage-independent growth and tumor formation, and triggered hyperphosphorylation of oncogenic PP2A-B56/B' substrates in the GSK3β, Akt and mTOR/p70S6K signaling pathways. TIPRL1 silencing restored GSK3β phosphorylation and rescued the EC cell growth advantage. Our results reveal how PPP2R1A mutations affect PP2A function and oncogenic signaling, illuminating the genetic basis for serous EC development and its potential control by rationally targeted therapies.

from Cancer via ola Kala on Inoreader http://ift.tt/2b1zXno
via IFTTT

Shp inhibition of HCC cell invasion via repressing Ccl2

Small heterodimer partner (SHP, NR0B2) is a nuclear orphan receptor without endogenous ligands. Due to its crucial inhibitory role in liver cancer, it is of importance to identify small molecule agonists of SHP. As such, we initiated a probe discovery effort to identify compounds capable of modulating SHP function. First, we performed binding assays using small molecule microarrays (SMMs) and discovered 5-(diethylsulfamoyl)-3-hydroxynaphthalene-2-carboxylic acid (DSHN) as a novel activator of SHP. DSHN transcriptionally activated Shp mRNA, but also stabilized SHP protein by preventing its ubiquitination and degradation. Second, we identified Ccl2 as a new SHP target gene by RNA-seq. We showed that activation of SHP by DSHN repressed Ccl2 expression and secretion by inhibiting p65 activation of CCL2 promoter activity, as demonstrated in vivo in Shp-/- mice and in vitro in HCC cells with SHP overexpression and knockdown. Third, we elucidated a strong inhibitory effect of SHP and DSHN on HCC cell migration and invasion by antagonizing the effect of CCL2. Lastly, by interrogating a publically available database to retrieve SHP expression profiles from multiple types of human cancers, we established a negative association of SHP expression with human cancer metastasis and patient survival. In summary, the discovery of a novel small molecule activator of SHP provides a therapeutic perspective for future translational and preclinical studies to inhibit HCC metastasis by blocking Ccl2 signaling.

from Cancer via ola Kala on Inoreader http://ift.tt/2b1zeST
via IFTTT

Active and Passive Macromolecule Targeting

Macromolecular reagents can be targeted to tumors through active and passive mechanisms. 'Active' targeting involves moieties, such as receptor ligands, to direct tumor cell binding, while 'passive' targeting relies on long reagent circulating half-life, abnormal tumor vasculature, and poor lymphatic drainage for tumor entrapment. Here we sought to study the impact of reagent circulating half-life on 'active' and 'passive' tumor uptake. The humanized PSMA-targeting antibody, HuJ591, was utilized as the 'active' targeting agent. HuJ591 was labeled with a Near Infrared (NIR) dye and its circulating half-life was modified by conjugation to high-molecular-weight Polyethylene Glycol (PEG). PEGylation did not negatively impact PSMA binding specificity. 'Active' and 'passive' tumor targeting of intravenously injected antibody conjugates were then quantified by NIR fluorescent imaging of immunocompromised mice bearing bilateral isogenic PSMA-positive and PSMA-negative human tumor xenografts. Two isogenic tumor pairs were applied, PC3 +/- PSMA (PC3-PIP/PC3-Flu) or LMD-MDA-MB-231 +/- PSMA (LMD-PSMA/LMD). This study provided a unique model system to simultaneously observe 'active' and 'passive' tumor targeting within a single animal. 'Passive' targeting was observed in all PSMA-negative tumors, and was not enhanced by enhanced size or extended circulating half-life. Interestingly, 'active' targeting was only successful in some situations. Both PSMA-positive tumor models could be actively targeted with J591-IR800 and J591-PEG10K. However, the larger J591-PEG30K enhanced 'active' targeting in the PC-3 tumor models, but inhibited 'active' targeting the LMD-MDA-MB-231 tumor model. Successful 'active' targeting was associated with higher PSMA expression. These results support the potential for 'active' targeting to enhance overall macromolecular reagent uptake within tumors.

from Cancer via ola Kala on Inoreader http://ift.tt/2agZ9Jl
via IFTTT

Inhibition of PolI and PIM in advanced prostate cancer

Purpose: The MYC oncogene is frequently over-expressed in prostate cancer (PC). Upregulation of ribosome biogenesis and function is characteristic of MYC-driven tumors. Additionally, PIM kinases activate MYC signaling and mRNA translation in PC and cooperate with MYC to accelerate tumorigenesis. Here, we investigate the efficacy of a single and dual approach targeting ribosome biogenesis and function to treat PC. Experimental Design: The inhibition of ribosomal RNA (rRNA) synthesis with CX-5461, a potent, selective and orally bioavailable inhibitor of RNA polymerase I (Pol I) transcription has been successfully exploited therapeutically, but only in models of hematological malignancy. CX-5461 and CX-6258, a pan-PIM kinase inhibitor, were tested alone and in combination in PC cell lines, in Hi-MYC and PTEN-deficient mouse models and in patient derived xenografts (PDX) of metastatic tissue obtained from a castration-resistant PC patient. Results: CX-5461 inhibited anchorage-independent growth and induced cell cycle arrest in PC cell lines at nanomolar concentrations. Oral administration of 50 mg/kg CX-5461 induced p53 expression and activity and reduced proliferation (Ki-67) and invasion (loss of ductal actin) in Hi-MYC tumors, but not in PTEN null (low MYC) tumors. While 100 mg/kg CX-6258 showed limited effect alone, its combination with CX-5461 further suppressed proliferation and dramatically reduced large invasive lesions in both models. This rational combination strategy significantly inhibited proliferation and induced cell death in PDX of PC. Conclusions: Our results demonstrate preclinical efficacy of targeting the ribosome at multiple levels and provide a new approach for the treatment of PC.

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

Alemtuzumab in adult T-cell leukemia

Purpose: Therapeutic regimens for ATL are limited with unsatisfactory results, thereby warranting development of novel therapies. This study investigated antitumor activity and toxicity of alemtuzumab with regard to response, duration of response, progression free survival, and overall survival in patients with human T-cell lymphotropic virus-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATL). Experimental Design: Twenty-nine patients with chronic, acute, and lymphomatous types of ATL were enrolled in a single institution, nonrandomized, open-label Phase II trial wherein patients received intravenous alemtuzumab 30 mg three times weekly for a maximum of 12 weeks. Results: Twenty-nine patients were evaluable for response and toxicity. The overall objective response was 15 out of 29 patients (95% CI: 32.5 to 70.6%). The 15 patients that responded manifested a median time to response of 1.1 months. Median response duration was 1.4 months for the whole group and 14.5 months among responders. Median progression free survival was 2.0 months. Median overall survival was 5.9 months The most common adverse events were 2 with vasovagal episodes (7%) and 3 with hypotensive episodes (10%), leukopenia (41%)grade 3 and (17%) grade 4, lymphocytopenia (59%) grade 3, neutropenia (31%) grade 3, anemia (24%) and thrombocytopenia 10%. All patients developed cytomegalovirus antigenemia (CMV). Three were symptomatic and all responded to antiviral therapy. Grade 3 or 4 infections were reported in 4 (14%) of patients. Conclusions: Alemtuzumab induced responses in patients with acute HTLV-1-associated ATL with acceptable toxicity, but with short duration of responses. These studies support inclusion of alemtuzumab in novel multi-drug therapies for ATL.

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

Preclinical 11C-Acetate-PET in multiple myeloma

Purpose:We hypothesized that in multiple myeloma cells (MMC), high membrane biosynthesis will induce acetate uptake in vitro and in vivo. Here, we studied acetate metabolism and targeting in MMC in vitro and tested the efficacy of ¹¹C-acetate-PET (positron emission tomography) to detect and quantitatively image myeloma treatment response in vivo. Experimental Design:Acetate fate tracking using ¹³C-edited-¹H NMR (nuclear magnetic resonance) was performed to study in vitro acetate uptake and metabolism in MMC. Effects of pharmacological modulation of acetate uptake or acetate incorporation into lipids on MMC cell survival and viability were assessed. Preclinical mouse MM models of subcutaneous and bone tumors were evaluated using ¹¹C-acetate-PET/CT imaging and tissue biodistribution. Results:In vitro, NMR showed significant uptake of acetate by MMC, and acetate incorporation into intracellular metabolites and membrane lipids. Inhibition of lipid synthesis and acetate transport was toxic to MMC, while sparing resident bone cells or normal B cells. In vivo, ¹¹C-acetate uptake by PET imaging was significantly enhanced in subcutaneous and bone MMC tumors compared to unaffected bone or muscle tissue. Likewise, ¹¹C-acetate uptake was significantly reduced in MM tumors after treatment. Conclusions:Uptake of acetate from the extracellular environment was enhanced in MMC and was critical to cellular viability. ¹¹C-acetate-PET detected the presence of myeloma cells in vivo, including uptake in intramedullary bone disease. ¹¹C-acetate-PET also detected response to therapy in vivo. Our data suggested that acetate metabolism and incorporation into lipids was crucial to MM cell biology and that ¹¹C-acetate-PET is a promising imaging modality for MM.

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

Regression of POLE mutated tumors with nivolumab

Purpose: The management of endometrial carcinoma no longer amenable to treatment with surgery or radiation has not improved significantly with modern chemotherapy. Alternative therapeutic options are desperately needed. Experimental Design: We describe 2 heavily pretreated patients with recurrent disease refractory to surgery, radiation and chemotherapy treated with the anti-PD1 immune check-point inhibitor nivolumab. Results: Patient # 1 harbored an ultra-mutated (Mutation Load/MB = 117.3, total mutations = 4660) tumor driven by mutation in the exonuclease domain of the DNA polymerase gene. Patient # 2 harbored a hyper-mutated tumor (Mutation Load/MB = 33.5, total mutations = 1037) due to a germinal MSH6 gene mutation. Both patients demonstrated a remarkable clinical response to the anti-PD1 immune check-point inhibitor nivolumab. Patients' clinical responses remain unchanged at the time of the writing of this report with no grade 3 or higher side-effects reported to date. Conclusions: Anti-PD1 inhibitors represent a novel treatment option for recurrent/metastatic ultra/hypermutated human tumors refractory to salvage treatment.

from Cancer via ola Kala on Inoreader http://ift.tt/2atrmI7
via IFTTT

Myelosuppression by chemotherapy in obese patients with gynecological cancers

Abstract

Purpose

The American Society of Clinical Oncology provides clinical practice guidelines for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer. The panel recommends that actual body weight should be used when selecting cytotoxic chemotherapy doses regardless of obesity status. However, there have been no reports regarding the appropriate cytotoxic chemotherapy dosing for obese Japanese patients with cancer.

Patients and methods

We collected data from 216 gynecological cancer patients who were treated with at least one course of a paclitaxel and carboplatin (TC) regimen or a docetaxel and carboplatin (DC) regimen at Niigata University Medical and Dental Hospital from July 2006 to April 2014. Patients were divided into three groups according to body mass index (BMI): obese (BMI ≥ 25), normal (BMI 18.5–24.9), and underweight (BMI < 18.5), as defined by the Japan Society for the Study of Obesity. We analyzed hematological toxicities by full weight-based chemotherapy in each group.

Results

The rates of grade 3/4 leukocytopenia, neutropenia, and thrombocytopenia were not significantly different among the three BMI groups on all patient analyses. For the TC regimen, the obese and normal groups had significantly lower leukocytopenia (grade 3/4) rates than did the underweight group. Also, significant positive correlations between BMI and the nadirs of leukocytes, neutrophils, platelets, and hemoglobin were observed. For the DC regimen, no significant difference was observed among the BMI groups and the rate of grade 3/4 hematological toxicities.

Conclusions

We did not observe stronger myelosuppression in obese cancer patients compared with non-obese cancer patients. Therefore, the cytotoxic chemotherapy dose should be calculated by the actual body weight and unnecessary dose reduction should be avoided.

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

BSA and ABCB1 polymorphism affect the pharmacokinetics of sunitinib and its active metabolite in Asian mRCC patients receiving an attenuated sunitinib dosing regimen

Abstract

Purpose

An attenuated dosing (AD) sunitinib regimen of 37.5 mg daily has been suggested to reduce the toxicity reported with the standard dosing regimen to metastatic renal cell carcinoma (mRCC) patients. The aim of this study was to characterize the population pharmacokinetic (PK) properties of sunitinib and SU12662, the active metabolite, in patients receiving the AD regimen and to ascertain significant covariates influencing PK parameters.

Methods

Thirty-one mRCC patients receiving AD sunitinib regimen were included. Plasma samples were collected on day 29 of each treatment cycle after the start of the therapy. Nonlinear mixed-effects modeling was applied to estimate the population PK properties of sunitinib and SU12662 as well as the effect of covariates on PK parameters. Monte Carlo simulation was also performed to predict the total trough level (TTL) of sunitinib and SU12662.

Results

Sunitinib population means for CL/F and V _d /F _central were 13.8 L/h and 1720 L, respectively. SU12662 population means for CL/F and V _d /F were 42.1 L/h and 1410 L, respectively. Body surface area (BSA) and ABCB1 polymorphism significantly influenced the CL/F variability of sunitinib: CL/F _parent = 13.8 × exp((BSA − 1.75) × 2.08 + (ABCB1 _genotype − 0.67) × 0.61), ABCB1—0: wild genotype, 1: mutant genotype. The effect size of ABCB1 mutant genotype and BSA greater than 1.75 m² in relation to sunitinib clearance was 31.14 % (p = 0.006) and 22.11 % (p = 0.011), respectively, relative to the reference group.

Conclusions

Adjusting doses of sunitinib according to BSA and ABCB1 polymorphism in Asian mRCC patients may be recommended for sufficient attainment of a target TTL of sunitinib and its metabolite.

from Cancer via ola Kala on Inoreader http://ift.tt/2aKzGI1
via IFTTT

CPP2-p16MIS treatment–induced colon carcinoma cell death in vitro and prolonged lifespan of tumor-bearing mice

Abstract

Background

Cell-penetrating peptides (CPPs) are a research hotspot due to their noninvasive delivery ability. Among the identified CPPs, the TAT and R8 peptides have been preferentially applied to transduction into different cells. However, this process is nonselective among various cells. Recent research suggested that CPP2 could selectively penetrate human colorectal cancer (CRC) cells.

Methods

Using in vitro experiments, the mean fluorescence intensity of fluorescein isothiocyanate–labeled CPPs (CPPs-FITC) incubated with different cell lines was compared to corroborate the colon tumor targeting ability of CPP2. The targeting ability of CPP2 was determined in the same way in tumor-bearing mice. We synthesized antitumor peptides by fusing CPP2 to the minimal inhibitory sequence of p16 (p16MIS), which had the ability to restore the function of lost p16, the expression of which was absent in tumor cell lines of various origins. The antitumor effect of the combined peptide was tested in both CRC cell lines and tumor-bearing mice.

Results

In each CRC cell line, the mean fluorescence intensity of CPP2-FITC was higher than that of the TAT-FITC (p < 0.001) and R8-FITC (p < 0.001) groups. CPP2-p16MIS, the targeting carrier, showed a higher antitumor response in the in vitro cell research. CPP2-p16MIS showed a prolonged mean lifespan of tumor-bearing mice, further characterizing its role in specific tumor-targeting ability in vivo. Survival analysis showed that the mice treated with CPP2-p16MIS had significantly longer survival than the mice treated with phosphate-buffered saline (p < 0.05) or those treated with control peptides, including the CPP2 (p < 0.05) and p16MIS (p < 0.05) groups.

Conclusion

CPP2 could more selectively penetrate CRC cells than TAT or R8 as well as effectively deliver the p16MIS to the tumor.

from Cancer via ola Kala on Inoreader http://ift.tt/2ayy2Gh
via IFTTT

Integrated molecular pathway analysis informs a synergistic combination therapy targeting PTEN/PI3K and EGFR pathways for basal-like breast cancer

Abstract

Background

The basal-like breast cancer (BLBC) subtype is characterized by positive staining for basal mammary epithelial cytokeratin markers, lack of hormone receptor and HER2 expression, and poor prognosis with currently no approved molecularly-targeted therapies. The oncogenic signaling pathways driving basal-like tumorigenesis are not fully elucidated.

Methods

One hundred sixteen unselected breast tumors were subjected to integrated analysis of phosphoinositide 3-kinase (PI3K) pathway related molecular aberrations by immunohistochemistry, mutation analysis, and gene expression profiling. Incidence and relationships between molecular biomarkers were characterized. Findings for select biomarkers were validated in an independent series. Synergistic cell killing in vitro and in vivo tumor therapy was investigated in breast cancer cell lines and mouse xenograft models, respectively.

Results

Sixty-four % of cases had an oncogenic alteration to PIK3CA, PTEN, or INPP4B; when including upstream kinases HER2 and EGFR, 75 % of cases had one or more aberration including 97 % of estrogen receptor (ER)-negative tumors. PTEN-loss was significantly associated to stathmin and EGFR overexpression, positivity for the BLBC markers cytokeratin 5/14, and the BLBC molecular subtype by gene expression profiling, informing a potential therapeutic combination targeting these pathways in BLBC. Combination treatment of BLBC cell lines with the EGFR-inhibitor gefitinib plus the PI3K pathway inhibitor LY294002 was synergistic, and correspondingly, in an in vivo BLBC xenograft mouse model, gefitinib plus PI3K-inhibitor PWT-458 was more effective than either monotherapy and caused tumor regression.

Conclusions

Our study emphasizes the importance of PI3K/PTEN pathway activity in ER-negative and basal-like breast cancer and supports the future clinical evaluation of combining EGFR and PI3K pathway inhibitors for the treatment of BLBC.

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

An exploration of men’s experiences of undergoing active surveillance for favourable-risk prostate cancer: A mixed methods study protocol

Abstract

Background

Prostate cancer is one of the most common male cancers worldwide. Active Surveillance (AS) has been developed to allow men with lower risk disease to postpone or avoid the adverse side effects associated with curative treatments until the disease progresses. Despite the medical benefits of AS, it is reported that living with untreated cancer can create a significant emotional burden for patients.

Methods/design

The aim of this study is to gain insight into the experiences of men eligible to undergo AS for favourable-risk PCa.

This study has a mixed-methods sequential explanatory design consisting of two phases: quantitative followed by qualitative. Phase 1 has a multiple point, prospective, longitudinal exploratory design. Ninety men diagnosed with favourable-risk prostate cancer will be assessed immediately post-diagnosis (baseline) and followed over a period of 12 months, in intervals of 3 month. Ninety age-matched men with no cancer diagnosis will also be recruited using peer nomination and followed up in the same 3 month intervals. Following completion of Phase 1, 10–15 AS participants who have reported both the best and worst psychological functioning will be invited to participate in semi-structured qualitative interviews. Phase 2 will facilitate further exploration of the quantitative results and obtain a richer understanding of participants' personal interpretations of their illness and psychological wellbeing.

Discussion

To our knowledge, this is the first study to utilise early baseline measures; include a healthy comparison group; calculate sample size through power calculations; and use a mixed methods approach to gain a deeper more holistic insight into the experiences of men diagnosed with favourable-risk prostate cancer.

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

Overexpression of the miR-141/200c cluster promotes the migratory and invasive ability of triple-negative breast cancer cells through the activation of the FAK and PI3K/AKT signaling pathways by secreting VEGF-A

Abstract

Background

The role of microRNA-200 (miR-200) family members in the migration and invasion of breast cancer is controversial. This study investigated the mechanisms by which the miR-200 family members modulated the migratory and invasive abilities of an aggressive triple-negative breast cancer (TNBC) cell line, MDA-MB-231.

Methods

The miR-200 family (miR-200b/200a/429 and miR-141/200c clusters) and green fluorescence protein (GFP) were transduced into MDA-MB-231 cells using a lentiviral system. Stable cells highly expressing the miR-200 family and GFP were isolated by puromycin selection and fluorescence-activated cell sorting. Gene expression was evaluated using real-time polymerase chain reaction (PCR) and reverse transcriptase-PCR (RT-PCR). The migratory and invasive abilities were assessed using trans-well and wound-healing assays. The secreted cytokines and growth factors in cultured media were quantified using a Bio-Plex200 multiplex array system. Western blot assays and immunofluorescence staining were conducted to investigate miR-200 family-regulated signaling pathways. The entire dataset obtained in this study was statistically evaluated using a one-way ANOVA followed by a t-test.

Results

The stable overexpression of the miR-200b/200a/429 or miR-141/200c cluster suppressed cell growth and significantly increased migration and invasion of MDA-MB-231 cells. miR-141/200c overexpression was more effective in decreasing cell growth and promoting migration and invasion of MDA-MB-231 cells than was miR-200b/200a/429 overexpression. In addition, the overexpression of the miR-200b/200a/429 or miR-141/200c cluster led to an increase in the phosphorylation of focal adhesion kinase (FAK) and protein kinase B (AKT). Chemical inhibitors of FAK and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT suppressed the migration and invasion of MDA-MB-231 cells that was enhanced by the overexpression of the miR-200b/200a/429 or miR-141/200c cluster. Compared to the miR-200b/200a/429 cluster-transduced MDA-MB-231 cells, the miR-141/200c cluster-transduced MDA-MB-231 cells exhibited a significant increase in vascular endothelial growth factor (VEGF)-A secretion and integrin-alphaV (integrin-αV) expression. Treatment with an anti-VEGF-A-neutralizing antibody inhibited the increase in migration and invasion in both the miR-200b/200a/429- and miR-141/200c-transduced MDA-MB-231 cells but significantly reduced the phosphorylation of FAK and AKT in only the miR-141/200c cluster-transduced MDA-MB-231 cells.

Conclusions

Taken together, our data demonstrate a mechanism in which the miR-141/200c cluster, through FAK- and PI3K/AKT-mediated signaling by means of increased VEGF-A secretion, promotes the migratory and invasive abilities of MDA-MB-231 cells.

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

Post-crizotinib management of effective ceritinib therapy in a patient with ALK -positive non-small cell lung cancer

Abstract

Background

We report the re-biopsied diagnosis of a patient with anaplastic lymphoma receptor tyrosine kinase (ALK)-positive lung adenocarcinoma successfully treated with ceritinib 450 mg/day taken with food following disease progression and gastrointestinal intolerance to crizotinib.

Case presentation

A 74-year old female patient initially diagnosed with ALK-negative lung adenocarcinoma responded to initial standard chemotherapy. The patient was subsequently re-tested by next generation sequencing (NGS) and found to have ALK EIF2AK3-ALK fusion, and responded to crizotinib, but ultimately progressed and showed intolerance to this ALK inhibitor. She was then successfully treated with ceritinib 450 mg/day taken with food, has not suffered from any further gastrointestinal side-effects, and remains on ceritinib treatment after 12 months.

Conclusions

Second-line ceritinib treatment, when administered at 450 mg/day with food, is both well tolerated and efficacious in a patient with previously treated lung adenocarcinoma who had discontinued crizotinib due to disease progression and gastrointestinal adverse effects (AEs).

from Cancer via ola Kala on Inoreader http://ift.tt/2ayysw3
via IFTTT

The fibronectin III-1 domain activates a PI3-Kinase/Akt signaling pathway leading to αvβ5 integrin activation and TRAIL resistance in human lung cancer cells

Abstract

Background

Fibronectin is a mechanically sensitive protein which is organized in the extracellular matrix as a network of interacting fibrils. The lung tumor stroma is enriched for fibronectin which is thought to contribute to metastasis and drug resistance. Fibronectin is an elastic, multi-modular protein made up of individually folded domains, some of which can stretch in response to increased mechanical tension. Very little is known about the relationship of fibronectin's unfolded domains to lung cancer resistance to chemotherapy. In the present study, we evaluated the impact of unfolding the first Type III domain of fibronectin (FnIII-1c) on TNF-related apoptosis inducing ligand (TRAIL) resistance.

Methods

NCI-H460 non-small cell lung cancer cells were treated with FnIII-1c then assessed for TRAIL-induced apoptosis. Subsequent analysis of FnIII-1c-mediated signaling pathways was also completed. Human non-small cell lung cancer tissue sections were assessed for the expression of vitronectin by immunohistochemistry.

Results

FnIII-1c inhibited TRAIL-induced activation of caspase 8 and subsequent apoptosis in NCI-H460 lung cancer cells. FnIII-1c treatment was associated with the activation of the phosphatidylinositol-3-kinase/alpha serine/threonine kinase (PI3K/Akt) pathway and the αvβ5 integrin receptor for vitronectin, both of which were required for TRAIL resistance. Immunohistochemical staining of sections from non-small cell lung cancers showed that vitronectin was localized around blood vessels and in the tumor-stroma interface.

Conclusions

Unfolding of Type III domains within the fibronectin matrix may promote TRAIL resistance through the activation of a PI3K/Akt/αvβ5 signaling axis and point to a novel mechanism by which changes in secondary structure of fibronectin contribute to cancer cell resistance to apoptosis.

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

Socio-economic deprivation: a significant determinant affecting stage of oral cancer diagnosis and survival

Abstract

Background

Many factors contribute to socioeconomic status (SES), yet in most survival studies only income is used as a measure for determining SES. We used a complex, composite, census-based metric for socioeconomic deprivation to better distinguish individuals with lower SES and assess its impact on survival and staging trends of oral cancers.

Methods

Oropharyngeal (OPC) and oral cavity cancer (OCC) cases were identified from the British Columbia cancer registry between 1981–2009 and placed into affluent and deprived neighborhoods using postal codes linked to VANDIX (a composite SES index based on 7 census variables encompassing income, housing, family structure, education, and employment). Stage and cancer-specific survival rates were examined by sex, SES, and time period.

Results

Approximately 50 % of OPC and OCC cases of both sexes resided in SES deprived neighborhoods. Numbers of cases have increased in recent years for all but OCC in men. The deprivation gap in survival between affluent and deprived neighborhoods widened in recent years for OPC and OCC in men, while decreasing for OPC and increasing slightly for OCC in women. Greater proportions of OCC cases were diagnosed at later stage disease for both sexes residing in deprived neighborhoods, a trend not seen for OPC.

Conclusion

SES remains a significant independent determinant of survival for both OPC and OCC when using a composite metric for SES. OPC survival rates among men have improved, albeit at slower rates in deprived communities. OCC screening programs need to be targeted towards SES-deprived neighborhoods where greater proportions of cases were diagnosed at a later stage and survival rates have significantly worsened in both sexes.

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

Reproducibility and uptake time dependency of volume-based parameters on FDG-PET for lung cancer

Abstract

Background

Volume-based parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), on F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) are useful for predicting treatment response in nonsmall cell lung cancer (NSCLC). We aimed to examine intra- and inter-operator reproducibility to measure the MTV and TLG, and to estimate their dependency on the uptake time.

Methods

Fifty NSCLC patients underwent preoperative FDG-PET. After an injection of FDG, the whole body was scanned twice: at the early phase (61.4 ± 2.8 min) and delayed phase (117.7 ± 1.6 min). Two operators independently defined the tumor boundary using three different delineation methods: (1) the absolute SUV threshold method (MTV_p and TLG_p; p = 2.0, 2.5, 3.0, 3.5), (2) the fixed% SUVmax threshold method (MTV_q% and TLG_q%; q = 35, 40, 45), and (3) the adaptive region-growing method (MTV_ARG and TLG_ARG). Parameters were compared between operators and between phases.

Results

Both the intra- and inter-operator reproducibility were high for all parameters using any method (intra-class correlation > 0.99 each). MTV_3.0 and MTV_3.5 resulted in a significant increase from the early to delayed phase (P < 0.05 for both), whereas MTV_2.0 and MTV_2.5 neither increased nor decreased (P = n.s.). All of the MTV_q% values significantly decreased over time (P < 0.01), whereas MTV_ARG and TLG with any delineation method increased significantly (P < 0.05).

Conclusions

High reproducibility of MTV and TLG was obtained by all of the methods used. MTV_2.0 and MTV_2.5 were the least sensitive to uptake time, and may be good alternatives when we compare images acquired with different uptake times, although applying constant uptake time is important for volume measurement.

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

On Children, Blood, and Cancer: A new section of PBC

from Cancer via ola Kala on Inoreader http://ift.tt/2b0eOts
via IFTTT

A song

from Cancer via ola Kala on Inoreader http://ift.tt/2afF5Hh
via IFTTT

Dosimetric impact of different bladder and rectum filling during prostate cancer radiotherapy

Abstract

Background

The aim of this study was to analyze the influence of volumetric changes of bladder and rectum filling on the 3D dose distribution in prostate cancer radiotherapy.

Methods

A total of 314 cone-beam CT (CBCT) image data sets from 19 patients were enrolled in this study. For each CBCT, the bladder and rectum were contoured and volume sizes were normalized to those on their original CT. The daily delivered dose was recalculated on the CBCT images and the doses to bladder and rectum were investigated. Linear regression analysis was performed to identify the mean dose change of the volume change using SPSS 19.

Results

The data show that the variances of the normalized volume of the bladder and the rectum are 0.13–0.58 and 0.12–0.50 respectively. The variances of V_70Gy, V_60Gy, V_50Gy, V_40Gy and V_30Gy of bladder are bigger than those of rectum for 17 patients. The linear regression analysis indicates a 10 % increase in bladder volume will cause a 5.6 % (±4.9 %) reduction in mean dose (p <0.05).

Conclusions

The bladder's volume change is more significant than that of the rectum for the prostate cancer patient. The rectum volume variations are not significant except for air bubbles, which change the shape and the position of the rectum. The bladder volume variations may cause dose changes proportionately. Monitoring the bladder's volume before fractional treatment delivery will be crucial for accurate dose delivery.

from Cancer via ola Kala on Inoreader http://ift.tt/2b0d4Rb
via IFTTT

Does segmentectomy really preserve the pulmonary function better than lobectomy for patients with early-stage lung cancer?

Abstract

Purpose

Recently, segmentectomy has been considered as an alternative to lobectomy in early peripheral non-small lung cancer (NSCLC); however, controversy has remained regarding the long-term functional advantage after segmentectomy. The aim of this study was to analyze the postoperative lung function after segmentectomy and lobectomy for non-small cell lung cancer.

Methods

Patients with p-T1aN0M0 NSCLC who had undergone segmentectomy (n = 37) or lobectomy (n = 33) were retrospectively analyzed. The ratios of postoperative to preoperative forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were defined as the recovery rates. The radiological lung volume and weight were evaluated before and more than 6 months after surgery, and the postoperative values were compared with the predicted values that were calculated from the preoperative values, subtracting the resected lobes or segments.

Results

The clinical characteristics, including the preoperative lung function showed no significant differences between the groups. No statistical differences were recognized in the trend lines for recovery ratios of FVC and FEV1.0 (P = 0.96 and P = 0.33). The recovery ratios for radiologic lung volume and weight showed no significant differences (P = 0.46 and P = 0.22). The postoperative lung volume and weight were almost the same as the predicted values after segmentectomy, whereas those after lobectomy were significantly higher than the predicted values.

Conclusions

No functional advantage for segmentectomy was observed during long-term follow-up, possibly due to compensatory lung growth after lobectomy.

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

Mesenchymal stem cells attenuate ischemia–reperfusion injury after prolonged cold ischemia in a mouse model of lung transplantation: a preliminary study

Abstract

Purpose

Mesenchymal stem cells (MSCs) suppress inflammation and immune responses. We conducted this study to find out if MSCs attenuate ischemia–reperfusion injury in a mouse model of lung transplantation.

Methods

C57BL/6J mouse lungs perfused with low-potassium dextran glucose solution were preserved at 4 °C for 18 h. Human MSCs were slowly injected into the left pulmonary artery of the lung grafts, and orthotopic left lung transplantation was then performed. The lung isografts were reperfused for 6 h, and bronchoalveolar lavage fluid (BALF) from the left lung graft was collected. We measured the protein concentration, cell count, and proinflammatory cytokine concentrations in the BALF.

Results

The protein concentration and cell count in the BALF were significantly lower in the MSC-administered grafts than in the PBS-administered controls. Concentrations of proinflammatory cytokines, including IL-1β, IL-17A, and TNF-α, in BALF tended to be lower in the MSC-administered grafts than in the controls, but the difference was not significant.

Conclusion

The pre-transplant administration of MSCs via the pulmonary artery of the lung graft attenuated ischemia–reperfusion injury after prolonged cold ischemia in this mouse model of lung transplantation.

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

Dosimetric impact of different bladder and rectum filling during prostate cancer radiotherapy

The aim of this study was to analyze the influence of volumetric changes of bladder and rectum filling on the 3D dose distribution in prostate cancer radiotherapy.

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

Re-irradiation for locoregionally recurrent tumors of the thorax: a single-institution, retrospective study

Re-irradiation (re-RT) of the thorax is challenging due to the impact of prior therapies on normal tissues, and there are few reports of definitive re-RT. The treatment toxicities and efficacy of re-RT are not...

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

Myelosuppression by chemotherapy in obese patients with gynecological cancers

Abstract

Purpose

The American Society of Clinical Oncology provides clinical practice guidelines for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer. The panel recommends that actual body weight should be used when selecting cytotoxic chemotherapy doses regardless of obesity status. However, there have been no reports regarding the appropriate cytotoxic chemotherapy dosing for obese Japanese patients with cancer.

Patients and methods

We collected data from 216 gynecological cancer patients who were treated with at least one course of a paclitaxel and carboplatin (TC) regimen or a docetaxel and carboplatin (DC) regimen at Niigata University Medical and Dental Hospital from July 2006 to April 2014. Patients were divided into three groups according to body mass index (BMI): obese (BMI ≥ 25), normal (BMI 18.5–24.9), and underweight (BMI < 18.5), as defined by the Japan Society for the Study of Obesity. We analyzed hematological toxicities by full weight-based chemotherapy in each group.

Results

The rates of grade 3/4 leukocytopenia, neutropenia, and thrombocytopenia were not significantly different among the three BMI groups on all patient analyses. For the TC regimen, the obese and normal groups had significantly lower leukocytopenia (grade 3/4) rates than did the underweight group. Also, significant positive correlations between BMI and the nadirs of leukocytes, neutrophils, platelets, and hemoglobin were observed. For the DC regimen, no significant difference was observed among the BMI groups and the rate of grade 3/4 hematological toxicities.

Conclusions

We did not observe stronger myelosuppression in obese cancer patients compared with non-obese cancer patients. Therefore, the cytotoxic chemotherapy dose should be calculated by the actual body weight and unnecessary dose reduction should be avoided.

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

BSA and ABCB1 polymorphism affect the pharmacokinetics of sunitinib and its active metabolite in Asian mRCC patients receiving an attenuated sunitinib dosing regimen

Abstract

Purpose

An attenuated dosing (AD) sunitinib regimen of 37.5 mg daily has been suggested to reduce the toxicity reported with the standard dosing regimen to metastatic renal cell carcinoma (mRCC) patients. The aim of this study was to characterize the population pharmacokinetic (PK) properties of sunitinib and SU12662, the active metabolite, in patients receiving the AD regimen and to ascertain significant covariates influencing PK parameters.

Methods

Thirty-one mRCC patients receiving AD sunitinib regimen were included. Plasma samples were collected on day 29 of each treatment cycle after the start of the therapy. Nonlinear mixed-effects modeling was applied to estimate the population PK properties of sunitinib and SU12662 as well as the effect of covariates on PK parameters. Monte Carlo simulation was also performed to predict the total trough level (TTL) of sunitinib and SU12662.

Results

Sunitinib population means for CL/F and V _d /F _central were 13.8 L/h and 1720 L, respectively. SU12662 population means for CL/F and V _d /F were 42.1 L/h and 1410 L, respectively. Body surface area (BSA) and ABCB1 polymorphism significantly influenced the CL/F variability of sunitinib: CL/F _parent = 13.8 × exp((BSA − 1.75) × 2.08 + (ABCB1 _genotype − 0.67) × 0.61), ABCB1—0: wild genotype, 1: mutant genotype. The effect size of ABCB1 mutant genotype and BSA greater than 1.75 m² in relation to sunitinib clearance was 31.14 % (p = 0.006) and 22.11 % (p = 0.011), respectively, relative to the reference group.

Conclusions

Adjusting doses of sunitinib according to BSA and ABCB1 polymorphism in Asian mRCC patients may be recommended for sufficient attainment of a target TTL of sunitinib and its metabolite.

from Cancer via ola Kala on Inoreader http://ift.tt/2aKzGI1
via IFTTT

The molecular mechanism of action of superactive human leptin antagonist (SHLA) and quadruple leptin mutein Lan-2 on human ovarian epithelial cell lines

Abstract

Introduction

A number of leptin receptor antagonists have been synthesised for therapeutic use, with pre-clinical tests suggesting their future use in anticancer therapy. To our knowledge, there are no data concerning the possible application of leptin receptor blockers in ovarian cancer.

Methods

In this study, we evaluated two leptin receptor antagonists: superactive human leptin antagonist (SHLA) and quadruple leptin mutein, Lan-2 (L39A/D40A/F41A/I42A), on cell proliferation (Alamar Blue test, BrdU assay), cell cycle gene (qPCR) and protein expression (Western blot) and cell signalling pathways (Western blot) in three different types of cell lines: OVCAR-3, CaOV-3 and HOSEpiC.

Results

Both receptor blockers had no effect on non-cancerous HOSEpiC cell line proliferation; however, both reversed the stimulatory effect of leptin on CaOV-3 cell line proliferation to control levels and to below control levels in OVCAR-3 cells. In metastatic carcinoma CaOV-3, both ObR antagonists had an inhibitory effect on the cdk2/cyclin D1 complex, while in serous carcinoma, OVCAR-3, they only had an effect on cdk2 and cdk4 protein expression. SHLA had an inhibitory effect on all investigated signalling pathways in OVCAR-3, while only on Stat3 in CaOV-3. Lan-2 had an inhibitory effect on Stat3 and ERK1/2 in CaOV-3, while in OVCAR-3 it only affected Akt protein phosphorylation.

Conclusion

Based on these results, we conclude that SHLA and Lan-2 are promising leptin receptor inhibitors which could be used to block leptin activity, eliminating its negative effects on activities related to carcinogenesis. However, the selection of a specific antagonist should be related to tumour type.

from Cancer via ola Kala on Inoreader http://ift.tt/2aq2Sp4
via IFTTT

The molecular mechanism of action of superactive human leptin antagonist (SHLA) and quadruple leptin mutein Lan-2 on human ovarian epithelial cell lines

Abstract

Introduction

A number of leptin receptor antagonists have been synthesised for therapeutic use, with pre-clinical tests suggesting their future use in anticancer therapy. To our knowledge, there are no data concerning the possible application of leptin receptor blockers in ovarian cancer.

Methods

In this study, we evaluated two leptin receptor antagonists: superactive human leptin antagonist (SHLA) and quadruple leptin mutein, Lan-2 (L39A/D40A/F41A/I42A), on cell proliferation (Alamar Blue test, BrdU assay), cell cycle gene (qPCR) and protein expression (Western blot) and cell signalling pathways (Western blot) in three different types of cell lines: OVCAR-3, CaOV-3 and HOSEpiC.

Results

Both receptor blockers had no effect on non-cancerous HOSEpiC cell line proliferation; however, both reversed the stimulatory effect of leptin on CaOV-3 cell line proliferation to control levels and to below control levels in OVCAR-3 cells. In metastatic carcinoma CaOV-3, both ObR antagonists had an inhibitory effect on the cdk2/cyclin D1 complex, while in serous carcinoma, OVCAR-3, they only had an effect on cdk2 and cdk4 protein expression. SHLA had an inhibitory effect on all investigated signalling pathways in OVCAR-3, while only on Stat3 in CaOV-3. Lan-2 had an inhibitory effect on Stat3 and ERK1/2 in CaOV-3, while in OVCAR-3 it only affected Akt protein phosphorylation.

Conclusion

Based on these results, we conclude that SHLA and Lan-2 are promising leptin receptor inhibitors which could be used to block leptin activity, eliminating its negative effects on activities related to carcinogenesis. However, the selection of a specific antagonist should be related to tumour type.

from Cancer via ola Kala on Inoreader http://ift.tt/2aq2Sp4
via IFTTT

Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumours

Abstract

Hyperbaric oxygen (HBO) therapy is widely used as an adjunctive treatment for various pathological states, predominantly related to hypoxic and/or ischaemic conditions. It also holds promise as an approach to overcoming the problem of oxygen deficiency in the poorly oxygenated regions of the neoplastic tissue. Occurrence of local hypoxia within the central areas of solid tumours is one of the major issues contributing to ineffective medical treatment. However, in anti-cancer therapy, HBO alone gives a limited curative effect and is typically not applied by itself. More often, HBO is used as an adjuvant treatment along with other therapeutic modalities, such as radio- and chemotherapy. This review outlines the existing data regarding the medical use of HBO in cancer treatment, with a particular focus on the use of HBO in the treatment of brain tumours. We conclude that the administration of HBO can provide many clinical benefits in the treatment of tumours, including management of highly malignant gliomas. Applied immediately before irradiation, it is safe and well tolerated by patients, causing rare and limited side effects. The results obtained with a combination of HBO/radiotherapy protocol proved to be especially favourable compared to radiation treatment alone. HBO can also increase the cytostatic effect of certain drugs, which may render standard chemotherapy more effective. The currently available data support the legitimacy of conducting further research on the use of HBO in the treatment of malignancies.

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

Second malignancy risk among pediatric, adolescent, and young adult survivors of fusion-positive and fusion-negative sarcomas: Results from the SEER database, 1992 through 2012

BACKGROUND

The current study builds on the hypothesis that cancer-predisposing germline mutations are less common among patients with fusion-positive (F+) sarcomas compared to those with fusion-negative (F-) sarcomas, resulting in a lower risk of developing second malignant neoplasms (SMNs) in those with F + sarcomas.

METHODS

Standardized incidence ratios (SIRs) for developing SMNs were evaluated in 4822 survivors of F + and 3963 survivors of F- sarcomas that were diagnosed between 1992 and 2012 in pediatric, adolescent, and young adult patients (aged birth-39 years) and reported in the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazards models (adjusted hazard ratio [aHR]) and competing risk methods (subhazard ratio [sHR]) were used to evaluate SMN risk in those with F- versus F + sarcomas while controlling for demographic and clinical variables.

RESULTS

SMN risk was found to be nearly 2-fold greater among survivors of F + sarcomas (SIR, 1.86; 95% confidence interval [95% CI], 1.48-2.30) and nearly 3-fold greater among survivors of F- sarcomas (SIR, 2.89; 95% CI, 2.30-3.59) compared with the reference population. Although SMN types were noted to be similar between the fusion groups, the rate of any SMN was noted to be greater among survivors of F- sarcomas (aHR, 1.38 [95% CI, 1.01-1.89] and sHR, 1.27 [95% CI, 0.94-1.73]) when compared with survivors of F + sarcomas. The difference was most notable for solid tumor SMNs after index sarcomas were diagnosed between 2002 and 2012, for which rates of SMN were >2-fold greater among survivors of F- sarcomas (aHR, 2.31 [95% CI, 1.20-4.48] and sHR, 2.24 [95% CI, 1.13-4.43]).

CONCLUSIONS

The findings of the current study highlight the increased SMN risk experienced by survivors of sarcoma and demonstrate higher SMN rates in survivors of F- sarcomas compared to those with a history of F + sarcomas. Cancer 2016. © 2016 American Cancer Society.

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

Frequency of psycho-oncologic and social service counseling in cancer centers relative to center site and hospital characteristics: Findings from 879 center sites in Germany, Austria, Switzerland, and Italy

BACKGROUND

There is extensive evidence that patients with cancer and cancer survivors have a strong need for expert support in relation to the psychological and social consequences of the disease. The requirements set out in the German Cancer Society's cancer center certification system include the routine provision of psycho-oncologic care (POC) and social service counseling for every patient. The current study investigated which organizational and structural characteristics in hospitals account for variations in psychosocial care provision in these centers.

METHODS

Data routinely collected during the certification process regarding the percentages of psychosocial care provision and characteristics of center sites and hospitals were matched with data with regard to size of the municipality, teaching hospital status, and institutional ownership. Linear multilevel regression analyses were performed to identify the characteristics of hospitals and center sites that were related to psychosocial care provision.

RESULTS

Substantial differences were found for different types of cancer (eg, a greater provision of psychosocial care in centers specializing in breast rather than prostate cancer). There was more POC provision in longer-certified centers and less in rural areas and university hospitals. Much of the variation between hospitals remains unexplained.

CONCLUSIONS

Although the implementation of mandatory psychosocial services generally provides patients with access to POC and social service counseling, the wide differences in the provision of counseling indicate that additional measures are needed to avoid inequalities resulting from the center at which a patient receives cancer treatment. Cancer 2016. © 2016 American Cancer Society.

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

Primary Soft Tissue Lymphomas: Description of Seven Cases and Review of the Literature

Abstract

The present study describes a series of primary soft tissue lymphomas, including immunohistochemical characterization by tissue microarray and cytogenetic profiling. Formalin-fixed, paraffin-embedded tissue samples were collected from patients who underwent soft tissue biopsy. Cases were selected according to the definition of primary soft tissue lymphoma as a lymphoid malignancy arising in soft tissues without evidence of other nodal or extranodal localization for a period of at least 6 months. Our series comprised seven patients with a mean age of 72 years. There were three diffuse large B-cell lymphomas (DLBCLs); one B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma; one DLBCL derived from follicular lymphoma; one ALK-negative anaplastic large cell lymphoma; and one follicular lymphoma. Immunohistochemical and molecular profiles were consistent with the histological diagnoses. The present study contributes to our knowledge about uncommon presentation of lymphoid neoplasms and confirms previously published clinical-pathological data. We present, for the first time, the complete immunohistochemical profile and molecular cytogenetic studies of these lymphoid neoplasms. A rare case of a primary soft tissue ALK-negative anaplastic large cell lymphoma is described in detail.

from Cancer via ola Kala on Inoreader http://ift.tt/2aOYg8K
via IFTTT

Exercise Promotion in Geriatric Oncology

Abstract

Evidence of the benefits of exercise for people with cancer from diagnosis through survivorship is growing. However, most cancers occur in older adults and little exercise advice is available for making specific recommendations for older adults with cancer. Individualized exercise prescriptions are safe, feasible, and beneficial for the geriatric oncology population. Oncology providers must be equipped to discuss the short- and long-term benefits of exercise and assist older patients in obtaining appropriate exercise prescriptions. This review provides detailed information about professionals and their roles as it relates to functional assessment, intervention, and evaluation of the geriatric oncology population. This review addresses the importance of functional status assessment and appropriate referrals to other oncology professionals.

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

Immune Checkpoint Blockade: A New Era for Non-Small Cell Lung Cancer

Abstract

Despite better understanding of it's molecular biology, non-small cell lung cancer (NSCLC) remains a challenging disease to treat. Unfortunately, treatment options are still very limited and prognosis for advanced disease is poor. Immune surveillance plays a crucial role in a host's defence against tumour cells, and this is particular relevant for lung cancer due to it's high somatic mutational load, which increases the chances for the immune system to recognize cancer cells as 'non-self'. Novel immunotherapies are emerging as an effective treatment for this disease. In this review, we present the data on immune checkpoint inhibitors for NSCLC, describing their mechanism of action, data efficacy from recent clinical trials, and strategies to select patients more likely to benefit from these agents.

from Cancer via ola Kala on Inoreader http://ift.tt/2aM4KYP
via IFTTT

Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer

Abstract

The role of adjuvant chemotherapy in stage T2-T3N0 colon cancer (CC) is controversial and there are currently no reliable factors allowing for individual selection of patients with high risk of relapse for such therapy. We searched for microRNA-based signature with prognostic significance in this group. We assessed by qRT-PCR expression of 754 microRNAs (miRNAs) in tumour samples from 85 stage pT2-3N0 CC patients treated with surgery alone. MiRNA expression was compared between two groups of patients: 40 and 45 patients who did and did not develop distant metastases after resection, respectively. Additionally, miRNA expression was compared between CC and normal colon mucosa samples and between the mismatch repair (MMR) competent and deficient tumours. Low expression of miR-1300 and miR-939 was significantly correlated with shorter distant metastasis-free survival (DMFS) in Cox univariate analysis (p.adjusted = 0.049). The expression signature of five miRNAs (miR-1296, miR-135b, miR539, miR-572 and miR-185) was found to be prognostic [p = 1.28E−07, HR 8.4 (95 % CI: 3.81–18.52)] for DMFS and cross-validated in a leave-one-out analysis, with the sensitivity and specificity of 74 and 78 %, respectively. The expression of miR-592 was significantly associated with the MMR status (p.adjusted <0.01). The expression of several novel miRNAs were found to be tumour specific, e.g. miR-888, miR-523, miR-18b, miR-302a, miR-423-5p, miR-582-3p (p < 0.05). We developed a miRNA expression signature that may be predictive for the risk of distant relapse in early stage CC and confirmed previously reported association between miR-592 expression and MMR status.

from Cancer via ola Kala on Inoreader http://ift.tt/2aoL3mp
via IFTTT

Exhaled Breath Condensate as a Source of Biomarkers for Lung Carcinomas. A Focus on Genetic and Epigenetic Markers – A Mini-Review

Abstract

Lung carcinoma is one of the most common causes of cancer-related mortality worldwide. It is an aggressive tumor, often diagnosed at an advanced stage when treatment options are limited. Currently, the importance of detection and assessment of various genetic alterations in cancer is recognized as they can serve as very helpful markers in early diagnosis and follow-up of treatment regimens. Recently, several therapeutically important genetic markers have been identified. One major problem is that tumor tissue specimens used to assay these genetic biomarkers are not always available, especially in the early stages of the disease. Therefore, exhaled breath condensates (EBC) could represent a good non-invasive source to allow the evaluation of these important genetic markers; these could help in the diagnosis, follow-up of the disease and/or assessment of treatment efficacy. The key aims of this review are firstly to describe the origin and constituents of EBC, as well as the different methodological procedures used in studying EBC biomarkers, and secondly, to document genetic and epigenetic markers that have been analyzed in EBC from lung cancer patients and to estimate their diagnostic and prognostic value. This article is protected by copyright. All rights reserved.

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

Cancers, Vol. 8, Pages 73: Developmental Drift and the Role of Wnt Signaling in Aging

Population aging is a public health problem affecting the majority of the developed world. As populations age, the incidence of degenerative diseases increases exponentially, leading to large increases in public spending on healthcare. Here we summarize recent findings on the developmental drift theory of aging, and the links that have been established between aging and the Wnt signaling pathways. We focus on insights derived from model organisms connecting the evolutionary basis of aging and the link to developmental programming.

from Cancer via ola Kala on Inoreader http://ift.tt/2as8rRn
via IFTTT