Cancer by Sfakianakis Alexandros: 08/09/17

Τετάρτη 9 Αυγούστου 2017

Beyond Genomics - Targeting the Epigenome in Diffuse Large B-Cell Lymphoma

Publication date: Available online 9 August 2017
Source:Cancer Treatment Reviews
Author(s): Andrea Kühnl, David Cunningham, Ian Chau
After decades of intense research on genetic alterations in cancer and successful implementation of genetically-based targeted therapies, the field of cancer epigenetics is only beginning to be fully recognized. The discovery of frequent mutations in genes modifying the epigenome in diffuse large B-cell lymphoma (DLBCL) has highlighted the outstanding role of epigenetic deregulation in this disease. Identification of epigenetically-driven DLBCL subgroups and development of novel epigenetic drugs have rapidly advanced. However, further insights are needed into the biological consequences of epigenetic alterations and the possibility of restoring the aberrant epigenome with specific therapies to bring this treatment concept further into clinical practice. This review will summarize the main epigenetic changes found in DLBCL and their potential for precision medicine approaches.

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Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma

Abstract

Purpose of Review

Prognosis of advanced oral squamous cell carcinoma remains a challenge for clinicians despite progress in its diagnosis and treatment over the past decades. In this review, we assessed clinicopathological factors and potential biomarkers along with their prognostic relevance in an attempt to develop optimal treatment strategies for these patients.

Recent Findings

In addition to several pathologic factors that have been proposed to improve prognostic stratification and treatment planning in the eighth edition of the American Joint Committee staging manual on cancer, we reviewed some other imaging and clinicopathological parameters demonstrated to be closely associated with patient prognosis, along with the biomarkers related to novel target or immune therapy.

Summary

Evaluation of current literature regarding the prognostic stratification used in contemporary clinicopathological studies and progress in the development of targeted or immune therapy may help these patients benefit from tailored and personalized treatment and obtain better oncological results.

http://ift.tt/2urlH42

Immunotherapy in Breast Cancer: the Emerging Role of PD-1 and PD-L1

Abstract

Purpose of Review

The purpose of the review is to summarize the data regarding PD-L1 expression in breast cancer and the results of first clinical trials with PD-1 or PD-L1 inhibitors in patients with metastatic breast cancer.

Recent Findings

PD-L1 expression is heterogeneous across primary breast cancers, and is generally associated with the presence of tumor-infiltrating lymphocytes and the presence of poor-prognosis features such as high grade, and aggressive molecular subtypes (triple-negative (TN), basal, HER2-enriched). Early phase clinical trials using PD-1 or PD-L1 inhibitors alone or in combination have shown objective tumor responses and durable long-term disease control, in heavily pre-treated patients, notably in the TN subtype.

Summary

Blockade of PD-1 or PD-L1 shows impressive antitumor activity in some subsets of breast cancer patients. Many clinical trials are ongoing in the metastatic and neoadjuvant setting, alone and in combination with chemotherapy, targeted therapy, radiotherapy, and/or other immune therapy. The identification of biomarkers predictive for a clinical benefit is warranted.

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A combination of anti-PD-L1 mAb plus Lm-LLO-E6 vaccine efficiently suppresses tumor growth and metastasis in HPV-infected cancers

Abstract

PD-1/PD-L1 immunotherapy is viewed as having clinical benefits in advanced cancers but is effective in only a few patients, suggesting that an efficient combination approach is needed to improve efficacy. Immunohistochemistry analysis indicated that PD-L1 expression was correlated with the E6 expression in tumors from 122 lung cancer patients. The poorest survival occurred in PD-L1-positive/E6-positive tumor. PD-L1 expression was increased by the expression of E6, but not the E7, oncoprotein in lung and cervical cancer cells. PD-L1 expression was responsible for E6-mediated colony formation and soft agar growth. Therefore, PD-L1 secreted from tumor cells may directly promote tumor progression, particularly in E6-positive tumors. Immune deficiency nude mice were used to test the possibility that combining anti-PD-L1 mAb with Lm-LLO-E6 vaccine could have a higher antitumor activity compared with anti-PD-L1 mAb or Lm-LLO-E6 vaccine alone. A greater antitumor activity was obtained with anti-PD-L1 mAb + Lm-LLO-E6 vaccine than with anti-PD-L1 mAb or Lm-LLO-E6 alone in subcutaneous and metastatic tumors induced by TL-1 and SiHa cells. The longest survival time for nude mice was observed in the anti-PD-L1 mAb + Lm-LLO-E6 vaccine group. In conclusion, an anti-PD-L1 mAb + Lm-LLO-E6 vaccine may be an efficient treatment for suppression of tumor growth and metastasis induced by HPV-infected cells.

We have provided evidence that an anti-PD-L1 mAb + Lm-LLO-E6 vaccine combination is an efficient therapeutic approach against HPV-infected NSCLC. In addition, the anti-PD-L1 mAb + Lm-LLO-E6 vaccine combination also efficiently suppresses SiHa cell-induced tumors in nude mice. Therefore, we suggest that anti-PD-L1 mAb + Lm-LLO-E6 vaccine combination therapy may have a greater clinical benefit than anti-PD-L1 or HPV DNA vaccine immunotherapy in cancer patients with HPV-infected tumors.

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Clinical outcomes of patients with epithelioid sarcomas: impact and management of nodal metastasis

Abstract

Purpose

An epithelioid sarcoma is a rare histological subtype of a soft tissue sarcoma with a high local recurrence rate, which frequently shows lymph node metastasis. However, because of the rarity of this tumor, the impact of nodal metastasis and its appropriate management remain unclear. The present study investigated the clinical outcomes of patients with epithelioid sarcomas, with a focus on lymph node metastasis.

Methods

We retrospectively evaluated the clinical outcomes of 27 patients with epithelioid sarcomas treated between 1985 and 2015. The log-rank test was used to assess the prognostic variables.

Results

The overall local recurrence rate was 33%, and the estimated overall 5-year survival rate was 62%. Hand and foot locations were associated with favorable overall survival. During the follow-up period, new nodal metastasis was noted in 14 patients (52%). The incidence of local recurrence was higher in patients with new nodal metastasis than in patients who did not develop nodal metastasis. The development of new nodal metastasis had a tendency to worsen survival; however, this association was not statistically significant. Lymphadenectomy did not affect overall survival.

Conclusions

Peripheral tumor location is associated with a better prognosis. The development of new nodal metastasis tends to be associated with poor prognosis; however, among patients with nodal metastasis, resection of the metastatic lesions has a low impact on survival.

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Patient characteristics and overall survival in patients with post-docetaxel metastatic castration-resistant prostate cancer in the community setting

Abstract

It is unclear how treatment sequencing for metastatic castration-resistant prostate cancer (mCRPC) affects real-world patient outcomes. We assessed treatment sequences, patient characteristics and overall survival (OS) in post-docetaxel mCRPC patients. mCRPC patients receiving second-line cabazitaxel or androgen receptor-targeted therapy (ART; abiraterone/enzalutamide) post-docetaxel were identified using electronic medical records. OS was assessed from second-line therapy initiation using Cox regressions adjusting for: metastases; prostate-specific antigen (PSA); hemoglobin; alkaline phosphatase (ALP); albumin; second-line therapy initiation year. Following docetaxel (n = 629), 123 (19.6%) and 506 (80.4%) patients received cabazitaxel and ART, respectively. One hundred and ninety-five patients received additional treatments thereafter (54 following cabazitaxel; 141 following ART). Although patients receiving second-line cabazitaxel versus ART had similar disease characteristics at first-line therapy initiation, at second-line therapy initiation they had higher mean PSA (386.6 vs. 233.9 ng/mL) and ALP (182.0 vs. 167.3 u/L), lower mean hemoglobin (10.8 vs. 11.5 g/dL), and more frequently had intermediate/high-risk Halabi scores (61.8 vs. 48.4%); all p < 0.05. Overall, crude survival was not significantly different. Among Halabi high-risk patients, adjusted median OS was significantly longer in patients receiving cabazitaxel versus ART (HR 0.48; 95% CI 0.24–0.93; p = 0.030). Low albumin and hemoglobin led to similar findings (HR 0.43; 95% CI 0.23–0.80; p = 0.0077; HR 0.60; 95% CI 0.40–0.90; p = 0.014). Most post-docetaxel patients received second-line ART. Patients receiving second-line cabazitaxel had more high-risk features; however, second-line cabazitaxel administered after docetaxel may improve OS in patients with Halabi high-risk scores or low albumin/hemoglobin.

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Diagnostic and Therapeutic Strategies for Patients with Malignant Epidural Spinal Cord Compression

Opinion statement

Malignant epidural spinal cord compression (MESCC) is an oncologic emergency with the potential for devastating consequences for patients if not promptly diagnosed and treated. MESCC is diagnosed by imaging. MRI is by far the most sensitive test, preferably with gadolinium. Once the diagnosis of MESCC is suspected, patients with neurologic deficits should receive prompt administration of dexamethasone with a 10-mg IV loading dose followed by 4 mg every 6 h. Quick taper is recommended once the definitive treatment is established. Consultation with medical oncology, radiation oncology, and neurosurgery is imperative in order to facilitate a multidisciplinary approach. Although spine surgery is the most effective method for relief of cord compression and is necessary if there is spinal instability, surgery is only used in selected patients because most patients have a poor overall condition and short life expectancy. Radiation therapy, therefore, is the most commonly used therapy for patients with MESCC after surgical decompression or in patients who are not surgical candidates. Conventional fractionated radiation alone can achieve modest neurologic outcomes in selected radiosensitive tumors. Radiosurgery techniques which deliver intense focal irradiation to a delimited area with imaging guidance and contoured radiation delivery to the shape of the tumor have recently emerged as increasing effective treatments in MESCC, especially in radioresistant tumors. Stereotactic radiosurgery and different radiation technologies have been studied in recent clinical trials.

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Dermatofibrosarcoma Protuberans

Opinion statement

Dermatofibrosarcoma protuberans (DFSP) is a slow growing tumor with a very low metastatic potential but with significant subclinical extension and great capacity for local destruction. Thus, the first surgeon approached with such challenging tumor must attempt to cure the patient with a method that spares healthy tissue and ensures an optimal oncological, functional, and esthetic result. The treatment of DFSP often requires a multidisciplinary approach. Depending on location, dermatologic surgeons, surgical oncologists, head and neck surgeons, neurosurgeons, plastic surgeons, and occasionally medical oncologists may be involved with the management. Mohs micrographic surgery (MMS) is the preferred method when available. In our institution, most of the DFSP cases are often advanced cases; thus, dermatologic surgeons obtain clear margins peripherally and other surgical specialties assist with resection of the fascia and any critical deeper structures. When MMS is not available, wide local excision (at least 2- to 3-cm margins of resection) with exhaustive pathologic assessment of margin status is recommended, and it is best to confirm tumor extirpation prior to any reconstruction. Subclinical extension of the tumor could be related to the size; how long it has been growing or histological markers that are unknown right now. No clinical trials comparing MMS vs WLE are available, and further research should be focused on these subjects as well as the use of imatinib and other targeted therapies for recurrent and metastatic tumors and for neoadjuvant treatment.

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Letter to the Editor: Implications of BRAF Mutations in dMMR Colorectal Cancers

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Lung cancer as a cardiotoxic state: a review

Abstract

As the overall survival of patients with lung cancer continues to increase, more cancer survivors are faced with the risk of developing treatment-related cardiovascular toxicities. The increased knowledge of the molecular biology of non-small cell lung cancer has led to new and more personalized treatments. Nevertheless, the usual chemotherapy schemes and radiation therapy induce cardiac toxicities that are frequently underappreciated or go unnoticed. Up to date, the majority of cardiotoxicity studies have been focused in breast cancer, but new treatments in lung cancer patients, such as immune checkpoint-blocking antibodies or tyrosine kinase inhibitors, may also exert these cardiac toxic effects and therefore demand of the close collaboration of oncologists and cardiologists, in order to be addressed. The aim of this review is to provide more detailed information in regard to drug-induced cardiac toxicity focused in non-small cell lung cancer patients.

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Recent Advances in the Classification and Treatment of Ependymomas

Opinion Statement

Ependymomas are a subgroup of ependymal glia-derived neoplasms that affect children as well as adults. Arising within any CNS compartment, symptoms at presentation can range from acute onset due to increased intracranial pressure to insidious myelopathy. The overall survival (OS) outcomes in adult patients across the subgroups is heterogeneous with subependymoma having an excellent prognosis often even in the absence of any treatment, whereas supratentorial ependymomas tend to be higher grade in nature and may have an OS of 5 years despite gross total resection and adjuvant radiation. The rarity of ependymal tumors, together still only representing 1.8% of all primary CNS tumors, has been a long-standing challenge in defining optimal treatment guidelines via prospective randomized trials. Retrospective studies have supported maximal safe resection, ideally gross total resection, as the optimal treatment with adjuvant radiation therapy proffering additional tumor control. The evidence for efficacy of chemotherapy and targeted agents in adult ependymomas is minimal. Recent investigations of the molecular, genetic, and DNA methylation profiles of ependymal tumors across all age groups and CNS compartments have identified distinct oncogenic gene products as well as nine molecular subgroups correlating with similar outcomes. The 2016 World Health Organization of Tumors of the Central Nervous System update addresses some of these findings, although their clinical significance has not yet been fully validated. There are inconsistent survival outcomes in retrospective studies for ependymomas graded as II versus III, bringing into question the validity of histologic grading which is subject to high interobserver variability in part due to inconsistent application of mitotic count parameters.

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Treatment of Lung Carcinosarcoma and Other Rare Histologic Subtypes of Non-small Cell Lung Cancer

Opinion statement

Lung carcinosarcoma (PCS) and other histological subtypes of non-small cell lung cancer, such as primary pulmonary lymphoma (PPL), pulmonary carcinoid (PC), and primary pulmonary lymphoepithelioma-like carcinoma (LELC), are rare. For their low incidence, the diagnosis and treatment are still controversial. Some patients only need surgery, while others may need chemotherapy, radiotherapy, or targeted therapy. In this paper, we retrospectively reviewed the literature of some rare histological subtype of NSCLC for the recent 20 years, and try to get some conclusions.

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Novel Agents in the Treatment of Thymic Malignancies

Opinion statement

The management of thymic tumours is a paradigm of multidisciplinary collaboration. Chemotherapy may be administered part of curative-intent sequential strategy integrating subsequent surgery or radiotherapy, or as an exclusive treatment if local treatment is not achievable. Recurrences of thymic epithelial tumors should be managed according to the same strategy as newly diagnosed tumors. Given the limited activity of cytotoxic agents in the advanced, refractory setting, novel and innovative agents are needed. The better understanding of thymic carcinogenesis may provide a rationale in this setting.

Targeted agents approved for other solid tumors that have shown activity in thymic tumors include mTOR, KIT inhibitors, as well as somatostatin analogues. Anti-angiogenic agent sunitinib may be considered a standard in advanced lines of treatment. Ongoing studies are assessing the opportunity of targeting emerging targets, including PI3K, CDK, and immune checkpoint PD-1/PD-L1.

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Hsa_circ_0045714 regulates chondrocyte proliferation, apoptosis and extracellular matrix synthesis by promoting the expression of miR-193b target gene IGF1R

Abstract

In recent years, some studies have been made on the effects of circular RNA (circRNA) in osteoarthritis (OA) and so on; however, its mechanisms remain to be further explored. Studies have shown that tumor necrosis factor-alpha can inhibit hsa_circ_0045714 expression in chondrocytes so as to upregulate miR-193b expression. Dual-luciferase reporter assay showed that insulin-like growth factor 1 receptor (IGF1R) is a key target gene of miR-193b. Hsa_circ_0045714 over-expression does not influence miR-193b expression, but can inhibit its transcriptional activity, thereby upregulating IGF1R expression. Hsa_circ_0045714 can promote the expression of type II collagen and aggrecan, and upregulate chondrocyte proliferation, while its linear sequences cannot. IGF1R has similar function, while miR-193b can inhibit the expression of type II collagen and aggrecan, and downregulate chondrocyte proliferation but enhance their apoptosis. IGF1R overexpression can reverse the effect of miR-193b, while miR-193b mimics or IGF1R siRNA can inhibit the function of hsa_circ_0045714. Therefore, hsa_circ_0045714 can regulate extracellular matrix synthesis as well as proliferation and apoptosis of chondrocytes by promoting the expression of miR-193b target gene IGF1R. The findings will provide new proofs for studies on the applications of circRNA in OA and other orthopedic diseases.

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DMKN contributes to the epithelial-mesenchymal transition through increased activation of STAT3 in pancreatic cancer

Summary

DMKN was first identified in relation to skin lesion healing and skin carcinoma. Recently, its expression has been associated with pancreatic cancer tumorigenesis, although its involvement remains poorly understood. Herein, we show that DMKN loss of function in Patu-8988 and PANC-1 pancreatic cancer cell lines results in reduced phosphorylation of signal transducer and activator of transcription-3 (STAT3), and increased activation of extracellular signal-regulated kinase (ERK1/2) and AKT serine/threonine kinase. This decreases the proliferation ability of pancreatic ductal adenocarcinoma (PDAC) cells. In addition, DMKN knockdown decreased the invasion and migration of PDAC cells, partially reversed the epithelial-mesenchymal transition, retarded tumor growth in a xenograft animal model by decreasing the density of microvessels, and attenuated the distance metastasis of human PDAC in a mouse model. Taken together, these data suggest that DMKN may be a potential prognostic biomarker and therapeutic target in pancreatic cancer.

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CENP-R acts bilaterally as a tumor suppressor and an oncogene in the two-stage skin carcinogenesis model

Abstract

CENP-R is a component of the CENP-O complex, including CENP-O, CENP-P, CENP-Q, CENP-R, and CENP-U and is constitutively localized to kinetochores throughout the cell cycle in vertebrates. CENP-R deficient chicken DT40 cells are viable and show very minor effect on mitosis. To investigate the functional roles of CENP-R in vivo, we generated CENP-R deficient mice (Cenp-r^-/-). Mice heterozygous or homozygous for Cenp-r null mutation are viable and healthy, with no apparent defect in growth and morphology, indicating Cenp-r is not essential for normal development. Accordingly, to investigate the role of the Cenp-r gene in skin carcinogenesis, we subjected Cenp-r^-/- mice to the DMBA/TPA chemical carcinogenesis protocol and monitored their tumor development. As a result, Cenp-r^-/- mice initially developed significantly more papillomas than control wild type mice. However, papillomas in Cenp-r^-/- mice showed a decrease of proliferative cells and an increase of apoptotic cells. As a result, they did not grow bigger and some papillomas showed substantial regression. Furthermore, papillomas in Cenp-r^-/- mice showed lower frequency of malignant conversion to squamous cell carcinomas. These results indicate Cenp-r functions bilaterally in cancer development: during early developmental stages, Cenp-r behaves as a tumor suppressor, but during the expansion and progression of papillomas it behaves as a tumor-promoting factor.

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The feasibility of prostate-specific membrane antigen positron emission tomography(PSMA PET/CT)-guided radiotherapy in oligometastatic prostate cancer patients

Abstract

Background

To investigate the efficacy and toxicity of 68Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA) PET-CT-guided RT in the treatment of oligometastatic prostate cancer retrospectively.

Methods

A total of 23 prostate cancer patients with biochemical relapse, of which 13 were castration sensitive (CS) and 10 castration resistant (CR), were treated with intensity-modulated and image-guided RT (IMRT-IGRT) on ≤3 metastases detected by ⁶⁸Ga PSMA PET-CT. Androgen deprivation therapy was continued in CR patients.

Results

A total of 38 metastases were treated. The involved sites were pelvic bone (n = 16), pelvic lymph nodes (n = 11), paraaortic lymph nodes (n = 6), ribs (n = 3) and vertebral body (n = 2). The median PSA prior to RT was 1.1 ng/mL (range 0.1–29.0 ng/mL). A median dose of 43.5 Gy (range 30–64 Gy) was delivered by IMRT-IGRT in 12–27 fractions. At a median follow-up of 7 months (range 2–17 months), 19 patients (83%) were in remission. Four patients (17%) developed distant recurrences. The actuarial 1-year LC, PFS and OS rates were 100, 51 (95% CI 8–83%) and 100%. Univariate analysis demonstrated a statistically significantly better PFS in CS patients as compared to CR patients (1-year PFS 67 vs. 0%, p < 0.01). One patient experienced grade 2 acute gastrointestinal toxicity. Grade 3 or more toxicity events were not observed.

Conclusions

By providing optimal LC, low toxicity and a promising PFS in CS patients, the current retrospective study illustrated that ⁶⁸Ga PSMA PET-CT-guided RT may be an attractive treatment strategy in patients with oligometastatic prostate cancer. Validation by randomized trials is eagerly awaited.

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The Effect of RGD/NGR Peptide Modification of Melanoma Differentiation-Associated Gene-7/Interleukin-24 on Its Receptor Attachment, an In Silico Analysis

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.

http://ift.tt/2wvqcbk

Risk adapted dose-intensified postoperative radiation therapy in prostate cancer patients using a simultaneous integrated boost technique applied with helical Tomotherapy

Abstract

Background

Postoperative adjuvant radiation therapy (ART) in T3 and R1 prostate cancer as well as salvage radiation therapy (SRT) in case of postoperative biochemical failure (BF) are established treatments. Dose-intensified postoperative radiation therapy (RT) schemes have shown superior biochemical control accompanied by increased toxicity rates. In our study we evaluate a novel risk adapted dose-intensified postoperative RT scheme.

Methods

A consecutive series of prostate cancer patients receiving postoperative RT after radical prostatectomy using helical Tomotherapy between 04/2012 and 04/2015 was analyzed retrospectively. RT was administered using a simultaneous integrated boost (SIB) to the area at risk (37 fractions of 1.9 Gy, total dose: 70.3 Gy) being defined based on histopathological findings (T3/R1 region) and in few cases according to additional diagnostic imaging. The whole prostate bed was treated with a dose of 66.6 Gy (37 fractions of 1.8 Gy). Primary endpoints were acute and late genitourinary (GU) and gastrointestinal (GI) toxicities. Secondary endpoints included patient reported outcome as assessed by the International Prostate Symptom Score (IPSS), the International Consultation on Incontinence questionnaire (ICIQ) and prostate cancer specific Quality of Life questionnaire QLQ-PR25, as well as rates of BF.

Results

A total of 69 patients were analyzed. Sixteen patients underwent ART and 53 patients SRT, respectively. The median follow-up was 20 months (range, 8–41 months). Seven (10.1%) and four (5.8%) patients experienced acute grade 2 GU and GI toxicity. Two patients (2.9%) had late grade 2 GU toxicity, whereas no late grade 2 GI nor any grade 3 acute or late GU or GI events were observed. When compared to the baseline IPSS scores (p = 1.0) and ICIQ scores (p = 0.87) were not significantly different at the end of follow-up. Patient reported Quality of life (QoL) showed also no significant difference. A total of seven patients (10.1%) experienced a biochemical recurrence with the 2-year biochemical progression-free survival (bPFS) being 91%.

Conclusions

Postoperative RT for prostate cancer patients with a risk adapted dose-intensified SIB using helical tomotherapy is feasible and associated with favorable acute and late GU and GI toxicity rates, no significant change of IPSS-, ICIQ scores and patient reported QoL and results in promising bPFS rates.

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The feasibility of prostate-specific membrane antigen positron emission tomography(PSMA PET/CT)-guided radiotherapy in oligometastatic prostate cancer patients

Abstract

Background

To investigate the efficacy and toxicity of 68Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA) PET-CT-guided RT in the treatment of oligometastatic prostate cancer retrospectively.

Methods

Results

Conclusions

http://ift.tt/2vQqDjg

The Effect of RGD/NGR Peptide Modification of Melanoma Differentiation-Associated Gene-7/Interleukin-24 on Its Receptor Attachment, an In Silico Analysis

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.

http://ift.tt/2wvqcbk

Atopy and prostate cancer: Is there a link between circulating levels of IgE and PSA in humans?

Abstract

Background

Atopy has been investigated as a potential risk factor for prostate cancer. IgE antibodies may be major players in protective responses against tumours, through engendering antigen presentation and enhancing adaptive immune responses targeted towards a specific allergen, but potentially also against tumour-associated antigens such as prostate-specific antigen (PSA). We therefore cross-sectionally investigated associations between circulating levels of PSA and IgE in the National Health and Nutrition Examination Survey 2005–2006.

Methods

We focused on all men aged 40+ years with measurements for PSA and IgE, and no previous diagnosis of prostate cancer (n = 1312). We estimated the association between total and specific IgE concentration and levels of PSA with logistic regression models, adjusted for age, ethnicity/race, education, smoking status, body mass index (BMI), physical activity status, and history of asthma.

Results

Both total IgE and the sum of specific IgE were inversely associated with the risk of having PSA levels ≥10 ng/mL, though most findings were not statistically significant. The odds ratios for the second and third tertile of total IgE as compared to the first were 0.21 (95% CI 0.06–0.72) and 0.42 (0.08–2.31). The odds ratio for sum of abnormal specific IgE measurements was 0.77 (0.44–1.34).

Conclusion

Despite statistical insignificance, the observed trend warrants further research given the increasing evidence of the role of atopy and IgE antibodies in protective responses against tumours. A lifecourse approach of measuring IgE, specific subtypes, and other markers of the humoral immune system (i.e. IgG) could shed more light on its potential anti-cancer characteristics.

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Atopy and prostate cancer: Is there a link between circulating levels of IgE and PSA in humans?

Abstract

Background

Methods

Results

Conclusion

http://ift.tt/2vnlHzt

An analysis of 97 previously diagnosed de novo adult acute erythroid leukemia patients following the 2016 revision to World Health Organization classification

Abstract

Background

The incidence of acute erythroid leukemia subtype (AEL) is rare, accounting for 5% of cases of acute myeloid leukemia (AML), and the outcome is dismal. However, in 2016 revision to the WHO classification, the subcategory of AEL has been removed. Myeloblasts are redefined as the percentage of total marrow cells, not non-erythroid cells. Therefore, the previously diagnosed AEL cases are currently diagnosed as AML or myelodyspalstic syndrome (MDS) according to new criteria.

Methods

We respectively reviewed cases of 97 de novo previously diagnosed AEL and all the patients were diagnosed as AML or MDS according to the new classification scheme, and then the clinical characteristics of these two subtypes were compared. Statistical analyses were performed by SPSS software version 18.0.

Results

The median age was 37 years-old, the two-thirds of previous AEL cases were diagnosed as MDS, and there was no obvious difference between two subtypes except for male/female ratio and age. Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. When the cytogenetic risk of patients belonged to MRC intermediate category and age were below 40 years-old in previous AEL cases, the patients who received induction chemotherapy without transplantation had a similar survival compared with the patients who underwent transplantation (3-year OS: 67.2% vs 68.5%).

Conclusions

Cytogenetic, rather than MDS/AML subtypes, can better represent the prognostic factor of previously diagnosed AEL patients. Transplantation was a better choice for those whose cytogenetic category was unfavorable.

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The effect of Nullomer-derived peptides 9R, 9S1R and 124R on the NCI-60 panel and normal cell lines

Abstract

Background

Nullomer peptides are the smallest sequences absent from databases of natural proteins. We first began compiling a list of absent 5-amino acid strings in 2006 (1). We report here the effects of Nullomer-derived peptides 9R, 9S1R and 124R on the NCI-60 panel, derived from human cancers of 9 organs (kidney, ovary, skin melanoma, lung, brain, lung, colon, prostate and the hematopoietic system), and four normal cell lines (endothelial HUVEC, skin fibroblasts BJ, colon epithelial FHC and normal prostate RWPE-1).

Methods

NCI-60 cancer cell panel and four normal cell lines were cultured in vitro in RPMI1640 supplemented with 10% Hyclone fetal bovine serum and exposed for 48 h to 5 μM, 25 μM and 50 μM of peptides 9R, 9S1R and 124R. Viability was assessed by CCK-8 assay. For peptide ATP depletion effects, one cell line representing each organ in the NCI-60 panel, and four normal cell lines were exposed to 50 μM of peptides 9R, 9S1R and 124R for 3 h. The ATP content was assessed in whole cells, and their supernatants.

Results

Peptides 9S1R and 9R are respectively lethal to 95 and 81.6% of the 60 cancer cell lines tested. Control peptide 124R has no effect on the growth of these cells. Especially interesting the fact that peptides 9R and 9S1R are capable of killing drug-resistant and hormone-resistant cell lines, and even cancer stem cells. Peptides 9R and 9S1R have a broader activity spectrum than many cancer drugs in current use, can completely deplete cellular ATP within 3 h, and are less toxic to 3 of the 4 normal cell lines tested than they are to several cancers.

Conclusions

Nullomer peptides 9R and 9S1R have a large broad lethal effect on cancer cell lines derived from nine organs represented in the NCI-60 panel. This broad activity crosses many of the categorical divisions used in the general classification of cancers: solid vs liquid cancers, drug sensitive vs drug resistant, hormone sensitive vs hormone resistant, cytokine sensitive vs cytokine non sensitive, slow growing vs rapid growing, differentiated vs dedifferentiated cancers. Furthermore peptides 9R and 9S1R are lethal to cancer stem cells and breast canrcinosarcoma.

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Lipopolysaccharide aggravated DOI-induced Tourette syndrome: elaboration for recurrence of Tourette syndrome

Abstract

Tourette syndrome (TS) is a neurological disorder characterized by highest familial recurrence rate among neuropsychiatric diseases with complicated inheritance. Recurrence of Tourette syndrome was frequently observed in clinical. Unexpectedly, the mechanism of recurrence of Tourette syndrome was failure to elucidate. Here, we first shown that lipopolysaccharide(LPS) may played an important role in the recurrence of Tourette syndrome. The TS model in rats was induced by DOI (the selective 5-HT2A/2C agonist 1-(2, 5-dimethoxy-4-iodophenyl) -2- aminopropane). The rats were randomly divided into 4 groups:(1)Control;(2) Control + LPS; (2)TS; (3)TS + LPS. The results demonstrated that the LPS treatment significantly increased stereotypic score and autonomic activity. LPS treatment also significantly increased inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum and striatum. Also, highly expressed TLR4, MyD88, P-NF-κBp65, P-IκBα in TS rats were increased respectively by LPS treatment as indicted in western blot analysis and immunohistochemistry analysis. Thus, it was supposed that lipopolysaccharide(LPS) may played an important role in the recurrence of Tourette syndrome and its mechanism was related to TLR/NF-κB pathway.

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The mean corpuscular volume as a prognostic factor for colorectal cancer

Abstract

Purpose

The aim of the present study was to identify the factors investigated during routine blood examinations which can predict the disease outcome independent of the tumor stage.

Methods

Data from 1174 patients with stage I, II, and III CRC who underwent R0 resection were included. We investigated the correlations between the preoperative routine blood examination data, and clinicopathological factors, and disease-free survival (DFS) using univariate and multivariate analyses.

Results

The univariate analysis showed that tumor location, tumor stage, CRP, serum albumin, creatine kinase, neutrophil-to-lymphocyte ratio, red blood cell count, mean corpuscular volume (MCV), and the administration of postoperative adjuvant chemotherapy were significantly correlated with the DFS. The multivariate analysis of the factors associated with the DFS showed that stage and MCV were significant factors; an MCV of <80 fL was associated with a superior DFS in comparison to an MCV of 80–100 fL (hazard ratio: 0.31, 95% confidence interval: 0.13–0.61, p = 0.0003). The DFS in patients with an MCV of <80 fL was superior to that in patients with an MCV of ≥80 fL, irrespective of whether the patients underwent postoperative adjuvant chemotherapy.

Conclusion

MCV was a prognostic factor for the DFS, independent of the tumor stage, in CRC patients who underwent R0 resection.

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Chronology of gastrointestinal cancer

Abstract

The "chronology of cancer" is a concept that describes the nature of cancers through the measure of time. The field extends from carcinogenesis to development, progression, and metastasis. Carcinogenesis is a multi-step process, which results from the accumulation of multiple genetic or epigenetic alterations. Various chronologies of gastrointestinal cancers have been reported for carcinogenesis caused by different risk factors. These chronologies are useful for developing cancer prevention strategies. The tumor growth rate is one of the most important factors in this field. Combining the factors of time and tumor growth enables us to estimate the time at which cancer or metastasis occurred, retrospectively, and to predict the survival of cancer patients, prospectively. It is noteworthy that these chronologies differ significantly among individual cases, even of cancers derived from the same organ. Thus, they are useful for individualization. We can apply the knowledge obtained in this field to the basic research and the diagnosis and treatment of cancers. The chronology of cancer is a classical but interesting field, which helps us consider and explore the essence of cancer. We review the topics related to the chronology of gastrointestinal cancer, ranging from carcinogenesis to metastasis.

http://ift.tt/2wJkm5q

Animals living in polluted environments are a potential source of anti-tumor molecule(s)

Abstract

Despite advances in therapeutic interventions and supportive care, the morbidity and mortality associated with cancer have remained significant. Thus, there is a need for newer and more powerful anti-tumor agents. The search for new anti-tumor compounds originating from natural resources is a promising research area. Animals living in polluted environments are a potent source of anti-tumor agents. Under polluted milieus, species such as crocodiles, feed on rotten meat, are exposed to heavy metals, endure high levels of radiation, and are among the very few species to survive the catastrophic Cretaceous-Tertiary extinction event with a prolonged lifespan. Thus, it is reasonable to speculate that animals such as crocodiles have developed mechanisms to defend themselves against cancer. The discovery of antitumor activity in animals such as crocodiles, whales, sharks, etc. will stimulate research in finding therapeutic molecules from unusual sources, and has potential for the development of novel antitumor compound(s) that may also overcome current drug resistance. Nevertheless, intensive research in the next few years will be required to realize these expectations.

http://ift.tt/2vnpHzK

The use of neoadjuvant therapy for resectable locally advanced thoracic esophageal squamous cell carcinoma in an analysis of 5016 patients from 305 designated cancer care hospitals in Japan

Abstract

Background

Recent studies have shown the benefits of neoadjuvant therapy with chemotherapy or chemoradiotherapy for resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC). The aim of our study was to elucidate the use of neoadjuvant therapy for thoracic ESCC in Japan.

Methods

Data on patients with stage IB–III thoracic ESCC were retrieved from the national database of hospital-based cancer registries combined with claims data between 2012 and 2013. These data were analyzed using a mixed-effect logistic regression analysis, with a focus on exploring patterns in the first-line treatment for ESCC, including proportion of patients who received neoadjuvant therapy, and investigating the hospital characteristics and patient factors associated with the use of neoadjuvant therapy.

Results

Of the 5016 patients with stage IB–III thoracic ESCC at the 305 participating hospitals, 34.2% received neoadjuvant therapy (neoadjuvant chemotherapy, 29.5%; neoadjuvant chemoradiotherapy, 4.7%). The therapy was less likely to be administered to older patients (≤64 years, 48.8%; 65–70 years, 42.0%; 70–75 years, 33.9%; 75–80 years, 22.2%; 80–85 years, 3.8%; ≥85 years, 1.4%) and at hospitals with a low volume of patients (very high, 42.1%; high, 37.5%; low, 30.7%; and very low, 26.4%). This trend was confirmed by regression analysis.

Conclusions

Based on our results, in Japan, relatively few patients with resectable locally advanced thoracic ESCC receive neoadjuvant therapy, with older patients and patients at lower volume hospitals being less likely than other patients to receive the neoadjuvant therapy. We recommend that the process of treatment decision-making be assessed at both the patient and hospital levels so that patients can consider various treatment options, including neoadjuvant therapy with surgery in Japan.

http://ift.tt/2vnyWAh

Drug resistance mutation profiles of the drug-naïve and first-line regimen-treated HIV-1-infected population of Suzhou, China

Abstract

Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance (TDR) and acquired drug resistance mutation (ADR) profiles, we collected blood specimens from 127 drug-naïve and 117 first-line drug-treated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified pol fragments from 100 drug-naïve and 20 drug-treated samples. We then determined the drug-resistant mutations to protease (PR) and reverse-transcriptase (RT) inhibitors according to the Stanford drug resistance database. Overall, 11 and 13 individuals had transmitted (drug-naïve group) and acquired (treated group) resistance mutations, respectively. Six transmitted drug-resistant mutations were found, including two mutations (L33F and L76V) in the protease region and four (K70N/E and V179D/E) in the RT region. Only L76V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine, and six had a treatment duration of less than three months. No major mutations to RT inhibitors were found, implying that the epidemic of transmitted resistance mutations was not significant in this area. Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment, especially for newly treated patients. Our research provides insights into the occurrence of HIV-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.

http://ift.tt/2wuSpyU

When is hemiarthroplasty preferable to intramedullary prophylactic fixation of malignant lesions of the proximal femur?

Background

Malignant hip lesions can be managed operatively by intramedullary (IM) nail fixation and hemiarthroplasty.

Methods

A retrospective review was performed on 86 patients who underwent hemiarthroplasty (n = 22) or IM nail fixation (n = 64) for prophylactic treatment of impending pathologic fracture due to malignant lesions of the hip. Cox proportional hazards and logistic regression modeling were performed to determine risk of death, fixation failure, pain relief, and return to ambulation without gait aids.

Results

Median survival time after surgery was 8.8 months (with no difference in survival between hemiarthroplasty and IM nail [adjusted Hazard Ratio 1.40, CI 0.72, 2.53; P = 0.31]). Hemiarthroplasty was associated with lower risk of pathologic fracture, fixation failure, or reoperation (adjusted HR 0.02, CI < 0.001, 0.48; P = 0.01). Hemiarthroplasty did not increase odds of unassisted ambulation compared to IM nail fixation (adjusted Odds Ratio [OR] 2.23, CI 0.56, 9.71; P = 0.26). The strongest predictor of postoperative ambulation was preoperative ambulation without aids (adjusted OR 28.9, CI 7.37, 161; P < 0.001).

Conclusions

There is no difference in survival or likelihood of unassisted ambulation after prophylactic femoral fixation with IM nails versus hemiarthroplasty in patients with metastatic disease of proximal femur.

http://ift.tt/2wJ4Lml

When is hemiarthroplasty preferable to intramedullary prophylactic fixation of malignant lesions of the proximal femur?

Background

Malignant hip lesions can be managed operatively by intramedullary (IM) nail fixation and hemiarthroplasty.

Methods

Results

Conclusions

http://ift.tt/2wJ4Lml

Detection of phosphatidylserine-positive exosomes for the diagnosis of early-stage malignancies

Detection of phosphatidylserine-positive exosomes for the diagnosis of early-stage malignancies

British Journal of Cancer 117, 545 (08 August 2017). doi:10.1038/bjc.2017.183

Authors: Raghava Sharma, Xianming Huang, Rolf A Brekken & Alan J Schroit

http://ift.tt/2t0a3fv

Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT promoter mutations in urine

Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT promoter mutations in urine

British Journal of Cancer 117, 583 (08 August 2017). doi:10.1038/bjc.2017.210

Authors: Françoise Descotes, Norelyakin Kara, Myriam Decaussin-Petrucci, Eric Piaton, Florence Geiguer, Claire Rodriguez-Lafrasse, Jean E Terrier, Jonathan Lopez & Alain Ruffion

http://ift.tt/2uwsbLF

Lifestyle predictors for non-participation and outcome in the second round of faecal immunochemical test in colorectal cancer screening

Lifestyle predictors for non-participation and outcome in the second round of faecal immunochemical test in colorectal cancer screening

British Journal of Cancer 117, 461 (08 August 2017). doi:10.1038/bjc.2017.189

Authors: Markus Dines Knudsen, Paula Berstad, Anette Hjartåker, Elisabeth Haagensen Gulichsen, Geir Hoff, Thomas de Lange, Tomm Bernklev & Edoardo Botteri

http://ift.tt/2uoAM69

MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer

MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer

British Journal of Cancer 117, 525 (08 August 2017). doi:10.1038/bjc.2017.181

Authors: P Zhang, W M Tang, H Zhang, Y Q Li, Y Peng, J Wang, G N Liu, X T Huang, J J Zhao, G Li, A M Li, Y Bai, Y Chen, Y X Ren, G X Li, Y D Wang, S D Liu & J D Wang

http://ift.tt/2sRjRbs

Geriatric assessment is superior to oncologists’ clinical judgement in identifying frailty

Geriatric assessment is superior to oncologists' clinical judgement in identifying frailty

British Journal of Cancer 117, 470 (08 August 2017). doi:10.1038/bjc.2017.202

Authors: Lene Kirkhus, Jūratė Šaltytė Benth, Siri Rostoft, Bjørn Henning Grønberg, Marianne J Hjermstad, Geir Selbæk, Torgeir B Wyller, Magnus Harneshaug & Marit S Jordhøy

http://ift.tt/2ssgbs2

LIM kinase 1 interacts with myosin-9 and alpha-actinin-4 and promotes colorectal cancer progression

LIM kinase 1 interacts with myosin-9 and alpha-actinin-4 and promotes colorectal cancer progression

British Journal of Cancer 117, 563 (08 August 2017). doi:10.1038/bjc.2017.193

Authors: Qing Liao, Rui Li, Rui Zhou, Zhihua Pan, Lijun Xu, Yanqing Ding & Liang Zhao

http://ift.tt/2ssf63t

Integrating cytokines and angiogenic factors and tumour bulk with selected clinical criteria improves determination of prognosis in advanced renal cell carcinoma

Integrating cytokines and angiogenic factors and tumour bulk with selected clinical criteria improves determination of prognosis in advanced renal cell carcinoma

British Journal of Cancer 117, 478 (08 August 2017). doi:10.1038/bjc.2017.206

Authors: A J Zurita, R C Gagnon, Y Liu, H T Tran, R A Figlin, T E Hutson, A M D'Amelio Jr, C N Sternberg, L N Pandite & J V Heymach

http://ift.tt/2uwkxkh

HYPE or HOPE: the prognostic value of infiltrating immune cells in cancer

HYPE or HOPE: the prognostic value of infiltrating immune cells in cancer

British Journal of Cancer 117, 451 (08 August 2017). doi:10.1038/bjc.2017.220

Authors: Tristan A Barnes & Eitan Amir

http://ift.tt/2uXl7ro

Harmonisation of biobanking standards in endometrial cancer research

Harmonisation of biobanking standards in endometrial cancer research

British Journal of Cancer 117, 485 (08 August 2017). doi:10.1038/bjc.2017.194

Authors: M Adishesh, A Fyson, S B DeCruze, J Kirwan, ENITEC Consortium, H M J Werner & D K Hapangama

http://ift.tt/2ssrUXv

UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins–TGF-β1–FAP-α

UV radiation promotes melanoma dissemination mediated by the sequential reaction axis of cathepsins–TGF-β1–FAP-α

British Journal of Cancer 117, 535 (08 August 2017). doi:10.1038/bjc.2017.182

Authors: Petra Wäster, Kyriakos Orfanidis, Ida Eriksson, Inger Rosdahl, Oliver Seifert & Karin Öllinger

http://ift.tt/2uOr2Pm

Kinase-driven metabolic signalling as a predictor of response to carboplatin–paclitaxel adjuvant treatment in advanced ovarian cancers

Kinase-driven metabolic signalling as a predictor of response to carboplatin–paclitaxel adjuvant treatment in advanced ovarian cancers

British Journal of Cancer 117, 494 (08 August 2017). doi:10.1038/bjc.2017.195

Authors: Maria Isabella Sereni, Elisa Baldelli, Guido Gambara, Antonella Ravaggi, K Alex Hodge, David S Alberts, Jose M Guillen-Rodriguez, Ting Dong, Maurizio Memo, Franco Odicino, Roberto Angioli, Lance A Liotta, Sergio L Pecorelli, Emanuel F Petricoin & Mariaelena Pierobon

http://ift.tt/2sWNEOJ

KIBRA attains oncogenic activity by repressing RASSF1A

KIBRA attains oncogenic activity by repressing RASSF1A

British Journal of Cancer 117, 553 (08 August 2017). doi:10.1038/bjc.2017.192

Authors: Anuj , Lakshmi Arivazhagan, Rohan Prasad Surabhi, Archana Kanakarajan, Sandhya Sundaram, Ravi Shankar Pitani, Lakmini Mudduwa, Joachim Kremerskothen, Ganesh Venkatraman & Suresh K Rayala

http://ift.tt/2ssc1jO

TOPK modulates tumour-specific radiosensitivity and correlates with recurrence after prostate radiotherapy

TOPK modulates tumour-specific radiosensitivity and correlates with recurrence after prostate radiotherapy

British Journal of Cancer 117, 503 (08 August 2017). doi:10.1038/bjc.2017.197

Authors: Giacomo Pirovano, Thomas M Ashton, Katharine J Herbert, Richard J Bryant, Clare L Verrill, Lucia Cerundolo, Francesca M Buffa, Remko Prevo, Iona Harrap, Anderson J Ryan, Valentine Macaulay, William G McKenna & Geoff S Higgins

http://ift.tt/2uHMXqy

Clinical study of genomic drivers in pancreatic ductal adenocarcinoma

Clinical study of genomic drivers in pancreatic ductal adenocarcinoma

British Journal of Cancer 117, 572 (08 August 2017). doi:10.1038/bjc.2017.209

Authors: Michael T Barrett, Ray Deiotte, Elizabeth Lenkiewicz, Smriti Malasi, Tara Holley, Lisa Evers, Richard G Posner, Timothy Jones, Haiyong Han, Mark Sausen, Victor E Velculescu, Jeffrey Drebin, Peter O'Dwyer, Gayle Jameson, Ramesh K Ramanathan & Daniel D Von Hoff

http://ift.tt/2tcPIjn

Modulating cancer cell survival by targeting intracellular cholesterol transport

Modulating cancer cell survival by targeting intracellular cholesterol transport

British Journal of Cancer 117, 513 (08 August 2017). doi:10.1038/bjc.2017.200

Authors: Omer F Kuzu, Raghavendra Gowda, Mohammad A Noory & Gavin P Robertson

http://ift.tt/2ufSCrZ

Pre-diagnostic statin use, lymph node status and mortality in women with stages I–III breast cancer

Pre-diagnostic statin use, lymph node status and mortality in women with stages I–III breast cancer

British Journal of Cancer 117, 588 (08 August 2017). doi:10.1038/bjc.2017.227

Authors: Amelia Smith, Laura Murphy, Lina Zgaga, Thomas I Barron & Kathleen Bennett

http://ift.tt/2tcEw6j

First cloned human immortalized adipose derived mesenchymal stem-cell line with chimeric SS18-SSX1 gene (SS-iASC)

Publication date: October 2017
Source:Cancer Genetics, Volumes 216–217
Author(s): Dóra Mihály, Zsolt Matula, Yi-Che Changchien, Gergő Papp, Péter Tátrai, Zoltán Sápi
The SS18-SSX chimeric gene is unique to synovial sarcoma. Multiple model systems including mouse cell lines expressing SS18-SSX, and genetically engineered mouse models of synovial sarcoma have been developed to elucidate the role of the chimeric gene in synovial sarcomagenesis. Although several cell lines stably expressing human SS18-SSX exist, there is an ongoing need for cell culture models enabling researchers to investigate the molecular mechanism of SS18-SSX action in a relevant cellular context. Here we report the establishment of a novel SS18-SSX1-expressing cell line created from immortalized human adipose tissue-derived mesenchymal stem cells via lentiviral transduction of the chimeric gene. Our cell line, termed SS-iASC, has been characterized by karyotyping and cell line identification, and stable expression of SS18-SSX1 has been verified using real-time PCR (RT-PCR), nested PCR, immunofluorescence, and immunoblotting. Focal cytokeratin positivity characteristic of synovial sarcoma but no β-Catenin, Bcl-2 or cyclin D1 expression was observed in SS-iASC. The novel cell line expressing SS18-SSX1 on a human adipose-derived stromal cell background is expected to be helpful in addressing the question whether the chimeric gene alone is sufficient to trigger the formation of synovial sarcoma.

http://ift.tt/2wuhaLB

RANK and EGFR in invasive breast carcinoma

Publication date: October 2017
Source:Cancer Genetics, Volumes 216–217
Author(s): Anastasios D. Papanastasiou, Chaido Sirinian, Eva Plakoula, Vassiliki Zolota, Ioannis K. Zarkadis, Haralabos P. Kalofonos
Breast cancer is the most common malignancy, affecting one in eight women in North America and Europe. The human epidermal growth factor receptor (EGFR) protein comprises a major determinant of normal development but also cancer. RANK receptor (Receptor Activator of Nuclear factor-κB) is a tumor necrosis superfamily member and a binding partner for RANKL, which was recently implicated in breast cancer initiation, progression and metastasis. Here we provide preliminary evidence of a possible interplay between RANK and EGFR signaling in breast cancer. TCGA (cancergenome.nih.gov) publicly available data for EGFR and TNFRSF11A (RANK) genes from breast cancer patients and breast cancer cell lines were retrieved and analyzed. RANK mRNA showed a statistically significant positive correlation (p < 0.001) with the mRNA and protein expression of EGFR, but not with ERBB2/3/4. Further analyses of survival data of a group of breast cancer patients (n = 248) from TCGA, revealed an EGFR^hi/RANK^hi subpopulation that showed a statistically significant (p = 0.001) reduced overall survival when compared to EGFR^low/RANK^low group of patients. Finally, EGFR and RANK combinatorial in vitro analyses revealed a significant upregulation of AKT and ERK signaling after EGF stimulation in cell lines and also an increase of breast cancer cell invasiveness.

http://ift.tt/2vjMBtI

Regret about surgical decisions among early-stage breast cancer patients:Effects of the congruence between patients’ preferred and actual decision-making roles

Abstract

Objective

Early-stage breast cancer patients generally receive either a mastectomy or a lumpectomy, either by their own choice or that of their surgeon. Sometimes there is regret about the decision afterward. To better understand regret about surgical decisions, this study examined two possibilities: The first is that women who take a dominant or collaborative role in decision- making about the surgery express less regret afterward. The second is that congruence between preferred role and actual role predicts less regret. We also explored whether disease stage moderates the relationship between role congruence and decisional regret.

Methods

In a cross-sectional design, 154 women diagnosed with breast cancer completed a survey assessing decisional role preference and actual decisional role, a measure of post-decision regret, and a measure of disturbances related to breast cancer treatment. Hierarchical regression was used to investigate prediction of decisional regret.

Results

Role congruence, not actual decisional role, was significantly associated with less decisional regret, independent of all the control variables. The interaction between disease stage and role congruence was also significant, showing that mismatch relates to regret only in women with more advanced disease.

Conclusions

Our findings suggest that cancer patients could benefit from tailored decision support concerning their decisional role preferences in the complex scenario of medical and personal factors during the surgical decision.

http://ift.tt/2vjf2aR

Is the LION strong enough?

Future Oncology, Ahead of Print.

http://ift.tt/2vO4NMx

Longitudinal parental preferences for late effects communication during cancer treatment

Abstract

Few studies have investigated parent preferences for late effects communication during pediatric cancer treatment. We used questionnaire data to assess whether parental preferences for late effects information change over the year after diagnosis. Most parents found this information to be very/extremely important at baseline, assessed soon after diagnosis, (94%, 153/162), 4 months (91%, 147/162), and 12 months (96%, 156/163). Similarly, most parents wanted as much detail as possible about late effects at baseline (85%, 141/165), 4 months (87%, 144/165), and 12 months (83%, 137/165). Parents of children with favorable prognoses preferred more details at baseline (OR 2.94, 1.18–7.31, P = 0.02) than parents whose children had less favorable prognoses.

http://ift.tt/2uoYorO

Multiple pilomatrixomas in a survivor of WNT-activated medulloblastoma leading to the discovery of a germline APC mutation and the diagnosis of familial adenomatous polyposis

Abstract

Because children diagnosed with WNT-activated medulloblastoma have a 10-year overall survival rate of 95%, active long-term follow-up is critically important in reducing mortality from other causes. Here, we describe an 11-year-old adopted female who developed multiple pilomatrixomas 3 years after diagnosis of WNT-activated medulloblastoma, an unusual finding that prompted deeper clinical investigation. A heterozygous germline APC gene mutation was discovered, consistent with familial adenomatous polyposis. Screening endoscopy revealed numerous precancerous polyps that were excised. This case highlights the importance of long-term follow-up of pediatric cancer survivors, including attention to unexpected symptoms, which might unveil an underlying cancer predisposition syndrome.

http://ift.tt/2uFF6d1

Rapid infusion of rituximab is well tolerated in children with hematologic, oncologic, and rheumatologic disorders

Abstract

Traditional administration of rituximab requires careful titration and may involve many hours to minimize the risk of reactions. The objective of this study was to evaluate the safety of rapid infusions of rituximab in a pilot group of children with hematologic, oncologic, and rheumatologic disorders, and to determine the incidence of rate-related infusion reactions. Twenty patients enrolled in the study. All patients tolerated the rapid infusion of rituximab and no patient had an infusion-related reaction. We conclude that rapid infusions of rituximab are well tolerated and safe in our pilot group of patients.

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Viral surveillance using PCR during treatment of AML and ALL

Abstract

Background

While viral surveillance of cytomegalovirus (CMV), Epstein–Barr virus (EBV), and adenovirus using PCR is routine in patients undergoing hematopoetic stem cell transplant and solid organ transplant, the utility in the nontransplant pediatric leukemia population is unknown. Our institution screens patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) for viral DNAemia by PCR as part of clinical care.

Procedure

This retrospective chart review included patients treated for newly diagnosed or relapsed AML or ALL between April 2010 and September 2014. We retrieved data for viral PCR screening, detection and quantification, duration of positivity, and prophylaxis or treatment.

Results

One hundred eleven patients were included in analyses. Forty (36.0%) had at least one blood PCR positive for EBV, CMV, or adenovirus. Patients with ALL had significantly higher rates of persistent viral detection and treatment than those with AML (P < 0.02, P < 0.01, respectively). International patients had significantly higher rates of viral detection (P < 0.01), persistence (P < 0.01), any treatment (P < 0.03), and antiviral treatment (P < 0.01); 16.9% of patients who received intravenous immunoglobulin (IVIG) prophylactically had viral detection compared to 63% of patients who did not receive prophylactic IVIG (P = 0.0008).

Conclusions

Patients with ALL were more susceptible than those with AML to viral reactivation that was persistent or resulted in treatment. Patients with relapsed ALL, refractory ALL, or infantile ALL are most likely to benefit from asymptomatic screening for CMV and adenovirus. International patients are at higher risk for reactivation and may merit screening. EBV reactivation was not significant and does not warrant screening.

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Reply to comment on: Generation and optimization of the self-administered pediatric bleeding questionnaire and its validation as a screening tool for von Willebrand disease

http://ift.tt/2up8EjJ

Molecular alterations in pediatric brainstem gliomas

Abstract

Background

Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis. Previously, diagnosis was based on a typical clinical presentation and magnetic resonance imaging findings. After the start of the era of biopsies, DIPGs bearing H3 K27 mutations have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27-mutated diffuse midline gliomas, and whether rare long-term survivors also belong to this group.

Methods

We studied tumor samples obtained at diagnosis or upon autopsy from 23 children, including two long-term survivors. Based on clinical, radiological, and histological findings, all tumors were previously diagnosed as DIPGs. All samples were analyzed for genetic alterations by next-generation sequencing (NGS) and for protein expression by immunohistochemistry (IHC).

Results

H3 K27 was mutated in NGS or IHC in 20 patients, excluding both long-term survivors. One of these long-term survivors harbored a mutation in IDH1, formerly considered to be an alteration absent in pediatric diffuse brainstem gliomas. Other altered genes in NGS included TP53 (10 patients), MET and PDGFRA (3 patients each), VEGFR and SMARCA4 (2 patients each), and PPARγ, PTEN and EGFR in 1 patient, respectively. IHC revealed cMYC expression in 15 of 24 (63%) of all samples, exclusively in the biopsies.

Conclusions

Eighty-seven percent of the tumors formerly diagnosed as DIPGs could be reclassified as H3 K27-mutated diffuse midline gliomas. Both long-term survivors lacked this alteration. Contrary to former conceptions, IDH1 mutations may occur also in pediatric brainstem gliomas.

http://ift.tt/2uGfqg9

Comparing oncologic outcomes after minimally invasive and open surgery for pediatric neuroblastoma and Wilms tumor

Abstract

Background

Minimally invasive surgery (MIS) has been widely adopted for common operations in pediatric surgery; however, its role in childhood tumors is limited by concerns about oncologic outcomes. We compared open and MIS approaches for pediatric neuroblastoma and Wilms tumor (WT) using a national database.

Methods

The National Cancer Data Base from 2010 to 2012 was queried for cases of neuroblastoma and WT in children ≤21 years old. Children were classified as receiving open or MIS surgery for definitive resection, with clinical outcomes compared using a propensity matching methodology (two open:one MIS).

Results

For children with neuroblastoma, 17% (98 of 579) underwent MIS, while only 5% of children with WT (35 of 695) had an MIS approach for tumor resection. After propensity matching, there was no difference between open and MIS surgery for either tumor for 30-day mortality, readmissions, surgical margin status, and 1- and 3-year survival. However, in both tumors, open surgery more often evaluated lymph nodes and had larger lymph node harvest.

Conclusion

Our retrospective review suggests that the use of MIS appears to be a safe method of oncologic resection for select children with neuroblastoma and WT. Further research should clarify which children are the optimal candidates for this approach.

http://ift.tt/2up5r3w

Erratum: De B, Kinnaman MD, Wexler LH, Kramer K, Wolden SL. Central nervous system relapse of rhabdomyosarcoma. Pediatr Blood Cancer. 2017; http://ift.tt/2uphWMv

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Predictors of remission in children with newly diagnosed immune thrombocytopenia: Data from the Intercontinental Cooperative ITP Study Group Registry II participants

Abstract

Background

Immune thrombocytopenia (ITP) during childhood spontaneously remits in up to 80% of children. Predictors of remission are not well understood.

Procedure

We analyzed data from Intercontinental Cooperative ITP Study Group (ICIS) Registry II, a large prospective cohort of children with ITP, to investigate factors that might predict remission.

Results

In ICIS Registry II, 705 patients had data collected through 12 months following diagnosis, with 383 patients having data available at 24 months as well. Younger age and pharmacologic treatment at diagnosis were significantly associated with disease resolution at 12 and 24 months (P < 0.0001 for both) as was bleeding at diagnosis (P < 0.0001 and P = 0.0213, respectively). Gender and platelet count at diagnosis were not significantly correlated with remission. In the multivariable analysis, remission at 12 months was associated with younger age, higher bleeding grade at diagnosis, and treatment with a combination of intravenous immunoglobulin (IVIG) and corticosteroids at diagnosis. Only younger age and treatment with IVIG and steroids in combination at diagnosis were associated with remission at 24 months. Patients <1 year of age had the highest odds of achieving remission at both 12 months (OR 4.7, 95% CI: 2.0–10.6) and 24 months (OR 7.0, 95% CI: 2.3–20.8).

Conclusions

Younger age, bleeding severity at diagnosis, and initial treatment with a combination of corticosteroids and IVIG are associated with remission at 12 months in the ICIS Registry II. Patients <1 year of age have the highest likelihood of remission. The relationship of bleeding and treatment at diagnosis requires further study to clarify whether these are independent predictors of remission.

http://ift.tt/2uG7nA5

Setup uncertainties and PTV margins at different anatomical levels in intensity modulated radiotherapy for nasopharyngeal cancer

Publication date: September–October 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 5
Author(s): Milan Anjanappa, Malu Rafi, Saju Bhasi, Rejnish Kumar, Kainickal Cessal Thommachan, Tapesh Bhattacharya, Kunnambath Ramadas
AimTo determine the systematic error (∑), random error (σ) and derive PTV margin at different levels of the target volumes in Nasopharyngeal Cancer (NPC).Materials and methodsA retrospective offline review was done for patients who underwent IMRT for NPC from June 2015 to May 2016 at our institution.Alternate day kV images were matched with digitally reconstructed radiographs to know the setup errors. All radiographs were matched at three levels – the clivus, third cervical (C3) and sixth cervical (C6) vertebra. The shifts in positions along the vertical, longitudinal and lateral axes were noted and the ∑ and σ at three levels were calculated. PTV margins were derived using van Herk's formula.ResultsTwenty patients and 300 pairs of orthogonal portal films were reviewed. The ∑ for the clivus, C3 and C6 along vertical, longitudinal and lateral directions were 1.6 vs. 1.8 vs. 2mm; 1.2 vs. 1.4 vs. 1.4mm and 0.9 vs. 1.6 and 2.3mm, respectively. Similarly, the random errors were 1.1 vs. 1.4 vs. 1.8mm; 1.1 vs. 1.2 vs. 1.2mm and 1.2 vs. 1.3 vs. 1.6mm. The PTV margin at the clivus was 4.4mm along the vertical, 4mm along the longitudinal direction and 3.2m in the lateral direction. At the C3 level, it was 5.5mm in the vertical, 5mm in the lateral direction and 4.4mm in the longitudinal direction. At the C6 level, it was 6.4mm in the vertical, 6.9mm in the lateral direction and 4.4mm in the longitudinal direction.ConclusionA differential margin along different levels of target may be necessary to adequately cover the target.

http://ift.tt/2upf0LL

Dual-Biomarker Blood Test Shows Promise for Pancreatic Cancer Early Detection

A new blood test that measures levels of two specific proteins may be able to accurately detect pancreatic cancer at its earliest stages, when it is most likely to respond to treatment, findings from a new study suggest.

http://ift.tt/2wHXBP6

A closer lens: Cancer survivors’ supportive intervention preferences and interventions received

Abstract

Background

Cancer survivor preferences for formal interventions designed to provide psychological support remain relatively unknown. To address this gap, we evaluated cancer survivors' preferences for psychological intervention, whom they preferred to recommend such intervention, and how their preferences compared with what they currently received.

Methods

U.S. cancer survivors (n = 345) who were at least 2 months post-treatment for diverse forms of cancer were recruited online to complete a survey study.

Results

Based on Wilcoxon signed-rank tests to distinguish among ranked preferences, cancer survivors rated individual professional counseling as their most-preferred form of psychological intervention, p < .001, followed by professionally-led cancer support groups and individual peer counseling. Anti-depressant or other psychiatric medication represented their least-preferred intervention (among 6 choices), ps < .001, but was the one they were most likely to currently receive. Preference for individual professional counseling over psychiatric medication was evident even among the subgroups of cancer survivors screening positively for probable anxiety disorder (n = 188) or major depression (n = 137), ps < .001. Cancer survivors most preferred to learn about psychological interventions from their medical oncologist, p < .001, followed by primary care physician, cancer nurse, or another cancer survivor; they least preferred to learn from a social worker or on their own, ps < .001.

Conclusions

Cancer survivors reported significant unmet need for psychological intervention, preference for non-pharmacological forms of such support, and a gap between their preferred forms of support and what they currently receive.

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Clinicopathological and prognostic significance of circulating tumor cells in patients with head and neck cancer: a meta-analysis

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Bystander signaling via oxidative metabolism

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Acute traumatic coagulopathy: pathophysiology and resuscitation

British Journal of Anaesthesia, 2016; 117(S3): iii31–iii43, DOI 10.1093/bja/aew328

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Cancers, Vol. 9, Pages 104: Complex Determinants of Epithelial: Mesenchymal Phenotypic Plasticity in Ovarian Cancer

Cancers, Vol. 9, Pages 104: Complex Determinants of Epithelial: Mesenchymal Phenotypic Plasticity in Ovarian Cancer

Cancers doi: 10.3390/cancers9080104

Authors: Yuliya Klymenko Oleg Kim M. Stack

Unlike most epithelial malignancies which metastasize hematogenously, metastasis of epithelial ovarian cancer (EOC) occurs primarily via transcoelomic dissemination, characterized by exfoliation of cells from the primary tumor, avoidance of detachment-induced cell death (anoikis), movement throughout the peritoneal cavity as individual cells and multi-cellular aggregates (MCAs), adhesion to and disruption of the mesothelial lining of the peritoneum, and submesothelial matrix anchoring and proliferation to generate widely disseminated metastases. This exceptional microenvironment is highly permissive for phenotypic plasticity, enabling mesenchymal-to-epithelial (MET) and epithelial-to-mesenchymal (EMT) transitions. In this review, we summarize current knowledge on EOC heterogeneity in an EMT context, outline major regulators of EMT in ovarian cancer, address controversies in EMT and EOC chemoresistance, and highlight computational modeling approaches toward understanding EMT/MET in EOC.

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Reconciling individual and population levels of porcine reproductive and respiratory syndrome virus evolution

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Selective A 2A receptor antagonist SCH 58261 modulates striatal oxidative stress and alleviates toxicity induced by 3-Nitropropionic acid in male Wistar rats

Abstract

The aim of the present study was to investigate the effects of SCH58261, a selective adenosine A_2A receptor antagonist, on striatal toxicity induced by 3-nitropropionic acid (3-NP) in rats. The experimental protocol consisted of 10 administrations (once a day) of SCH58261 (0.01 or 0.05 mg/kg/day, intraperitoneal, i.p.). From 7th to 10th day, 3-NP (20 mg/kg/day, i.p.) was injected 1 h after SCH58261 administration. Twenty-four hours after the last 3-NP injection, the body weight gain, locomotor activity (open-field test), motor coordination (rotarod test), striatal succinate dehydrogenase (SDH) activity and parameters linked to striatal oxidative status were evaluated in rats. The marked body weight loss resulting from 3-NP injections in rats was partially protected by SCH 58261 at both doses. SCH 58261 at the highest dose was effective against impairments on motor coordination and locomotor activity induced by 3-NP. SCH 58261 was unable to restore the inhibition of SDH activity caused by 3-NP. In addition, the increase in striatal reactive species (RS) levels, depletion of reduced glutathione (GSH) content and stimulation of glutathione reductase (GR) activity provoked by 3-NP injections were alleviated by both doses of SCH 58261. The highest dose of SCH 58261 was also effective in attenuating the increase of protein carbonyl levels as well as the inhibition of glutathione peroxidase (GPx) activity in rats exposed to 3-NP. Our results revealed that reduction of oxidative stress in rat striatum by adenosine A_2A receptor antagonism contributes for alleviating 3-NP-induced toxicity.

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A novel APC promoter 1B deletion shows a founder effect in Italian patients with classical familial adenomatous polyposis phenotype

Abstract

Familial adenomatous polyposis is a Mendelian syndrome in which germline loss-of-function mutations of APC are associated with multiple adenomatous polyps of the large bowel, a multiplicity of extracolonic features, and a high lifetime risk of colorectal cancer. Different APC germline mutations have been identified, including sequence changes, genomic rearrangements, and expression defects. Recently, very rare families have been associated with constitutive large deletions encompassing the APC-5' regulatory region, while leaving the remaining gene sequence intact; the regulatory region contains a proximal and a distal promoter, called 1A and 1B, respectively. We identified a novel deletion encompassing promoter 1B in a large Italian family that manifested polyposis in three of the six branches descending from a founding couple married in 1797. By combining different molecular approaches on both DNA and RNA, we precisely mapped this deletion (6,858 bp in length) that proved to be associated with APC allele silencing. The finding of the same deletion in two additional polyposis families pointed to a founder mutation in Italy. Deletion carriers from the three families all showed a "classical" polyposis phenotype. To explore the molecular mechanisms underlying promoter deletions, we performed an in silico analysis of the breakpoints of 1A and 1B rearrangements so far reported in the literature; moreover, to decipher genotype-phenotype correlations, we critically reviewed current knowledge on deletions vs. point mutations in the APC-5' regulatory region. This article is protected by copyright. All rights reserved.

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Perioperative Patient Beliefs Regarding Potential Effectiveness of Marijuana (Cannabinoids) for Treatment of Pain: A Prospective Population Survey.

Background and Objectives: Cannabinoids have an expanding presence in medicine. Perioperative patients' perceptions of the effectiveness of these compounds, and acceptance if prescribed for pain, have not been previously described. Our primary objective was to describe patients' beliefs regarding the potential effectiveness of cannabinoids for the treatment of acute and chronic pain, as well as gauge patient acceptance of these compounds if prescribed by a physician. In addition, demographic and pain history data were collected to elucidate the predictors of the aforementioned patient attitudes. Secondarily, we sought to characterize the subgroup of patients who reported marijuana use. Predictors of marijuana use, effectiveness, and adverse effects were also reported for this subgroup. Methods: An anonymous questionnaire was administered to 501 patients in the preoperative registration area at Mount Sinai Hospital, New York, New York. The questionnaire was designed to collect data on patient demographics, presence of pain, pain severity, use of pain medication, history of illicit-drug use, tobacco use, cannabis use, patient beliefs about the potential effectiveness of marijuana for acute and chronic pain and their willingness to use cannabis for pain, if prescribed by a physician. Normality of distributions for continuous variables was assessed with skewness and kurtosis measures. A logistic regression model was used to assess the demographic and medical characteristics of marijuana users compared with nonusers. The effectiveness of marijuana in dealing with pain and adverse effects associated with its use were examined using exploratory principal component analysis. Results: More than 80% of this cohort of preoperative patients believed that marijuana could be at least somewhat effective for the treatment of pain after surgery and would be willing to use cannabinoid compounds if prescribed by their physician. Predictors of positive attitudes toward marijuana included history of marijuana use, pain history, and being a marijuana nonuser of white race. Approximately 27% of the respondents reported a history of marijuana use. Younger patients, those with higher levels of pain in the last 24 hours, and those who found standard therapies to be less effective for their pain were more likely to use marijuana. Conclusions: Patients generally believe that marijuana could be at least somewhat effective for the management of pain and are willing to use cannabinoid compounds for this indication, if prescribed by a physician. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

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Use of antidepressants and risk of epithelial ovarian cancer

Abstract

Antidepressants are widely prescribed among women to treat depression and anxiety disorders, but studies of their effects on gynecological cancer risk are sparse. We assessed associations between various antidepressants and risk of epithelial ovarian cancer. By using Danish nationwide registers, we identified all women (cases) aged 30 to 84 years with incident epithelial (serous, endometrioid, clear cell or mucinous) ovarian cancer during 2000-2011 (n= 4,103) and matched each case to 20 population controls (n=58,706) by risk-set matching. Data on drug use (including tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants, and potential confounder drugs), medical and reproductive history, and socioeconomic parameters, were obtained from nationwide registries. We used conditional logistic regression models to estimate adjusted odds ratios (ORs) and two-sided 95% confidence intervals (CIs) for epithelial ovarian cancer associated with antidepressive drug use. Compared with non-use, use of selective serotonin reuptake inhibitors was associated with a decreased risk of ovarian cancer (OR, 0.85; 95% CI, 0.74-0.96), whereas the associations for other antidepressants were close to unity [tricyclic and related antidepressants: OR, 0.99 (95% CI, 0.78-1.26); other antidepressants: OR, 1.05 (95% CI, 0.76-1.46)]. For individual types of SSRI, reduced ORs were observed for citalopram OR, 0.78 (95% CI, 0.66-0.93), paroxetine 0.79 (95% CI, 0.56-1.12) and sertraline 0.80 (95% CI, 0.60-1.08). Among postmenopausal women, the inverse association was restricted to users of menopausal hormone therapy. In conclusion, use of selective serotonin reuptake inhibitors was associated with a decreased risk of epithelial ovarian cancer; thereby implying potential chemopreventive properties of these drugs. This article is protected by copyright. All rights reserved.

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Circulating mitochondrial Stress-70 protein/mortalin and cytosolic Hsp70 in blood: Risk indicators in colorectal cancer

Abstract

Mitochondrial mortalin and cytosolic Hsp70 are essential chaperones overexpressed in cancer cells. Our goals were to reproduce our earlier findings of elevated circulating levels of mortalin and Hsp70 in colorectal cancer (CRC) patients with a larger patient cohort, to compare death risk assessment of mortalin, Hsp70, CEA and C19-9 and to assess their prognostic value in various CRC stages. Mortalin, Hsp70, CEA and CA19-9 levels were determined in sera of 235 CRC patients enrolled in the study and followed-up 5 years after surgery. Association between their concentrations and patients' survival was analyzed by Kaplan-Meier estimator and subjected to Cox Proportional hazards analysis. Serum level of mortalin was independent of that of Hsp70, CEA and CA19-9, whereas Hsp70 level weakly correlated with CEA and CA19-9 levels. Improved short-term survival was found in early or advanced disease stages associated with lower mortalin and Hsp70 levels. Cox regression analysis showed a high mortality hazard (HR=3.7, P<0.001) in patients with both high mortalin and Hsp70 circulating levels. Multivariate analysis showed that high mortalin and Hsp70 significantly enhances risk score over a baseline model of age, number of affected lymph nodes, CEA, CA19-9, disease stage and perioperative therapy. Analysis of mortalin and Hsp70 in CRC patients' sera adds a high prognostic value to TNM stage and to CEA and CA19-9 and identifies patients with a lower or higher survival probability in all CRC stages. Determination of mortalin and Hsp70 in blood could be a useful additive prognostic tool in guiding clinical management of patients. This article is protected by copyright. All rights reserved.

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Sleep characteristics, light at night and breast cancer risk in a prospective cohort

Abstract

Increasing numbers of women in the US are getting too little sleep. Inadequate sleep has been associated with impaired metabolic function and endocrine disruption. Sister Study cohort participants (n=50,884), completed baseline and follow-up questionnaires on sleep patterns. Incident breast cancers estrogen receptor (ER) status of the tumor were ascertained from questionnaires and medical records. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). Analyses of sleep characteristics reported at the first follow-up interview included only participants who were breast cancer-free at time of follow-up interview. Over ∼7 years of follow-up, 2,736 breast cancer cases (invasive and ductal carcinoma in situ) were diagnosed. There was little evidence that usual sleep duration or other sleep characteristics were associated with breast cancer. However, relative to those with no difficulty sleeping, women who reported having difficulty sleeping ≥ 4 nights a week were at an increased risk of overall (HR=1.32, 95% CI: 1.09-1.61) and postmenopausal breast cancer (HR=1.51, 95% CI 1.24-1.85). Risk of ER+ invasive cancer was elevated for women who reported having a light or television on in the room while sleeping (HR=1.20, 95% CI: 0.97-1.47) or who typically got less sleep than they needed to feel their best (HR=1.21, 95% CI: 0.98-1.50). In our study, most sleep characteristics, including sleep duration, were not associated with an increased risk although higher risk was observed for some markers of inadequate or poor quality sleep. This article is protected by copyright. All rights reserved.

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The association of genetic variations in DNA repair pathways with severe toxicities in NSCLC patients undergoing platinum-based chemotherapy

Abstract

Genetic variations in genes involved in repairing platinum-induced DNA lesions may contribute to the toxicity of platinum-based chemotherapy. The role of single nucleotide polymorphisms (SNPs) within DNA repair pathways in the occurrence of severe toxicity is not yet understood. Current studies prefer to do original works rather than analyze previously published data. Our study aimed to replicate associations between previously investigated SNPs and toxicities as well as to identify new genetic makers. We systematically examined the relevance of 97 SNPs in 54 candidate genes responsible for repairing DNA inter-strand and intra-strand crosslinks to severe toxicity in a discovery cohort of 437 NSCLC patients receiving platinum-based chemotherapy. Statistically significant SNPs were then assessed for replication in an independent validation cohort of 781 NSCLC patients. We found that 7 SNPs were significant at P<0.01 (RRM1 rs12806698, XPC rs2228000, XPF rs1799801, hMLH1 rs1800734, PMS2 rs1062372, REV3L rs462779, and FANCC rs4647554) in the discovery cohort. Among them, two SNPs (RRM1 rs12806698 and hMLH1 rs1800734) remained significant after Bonferroni correction. XPC rs2228000 showed a significant relationship with gastrointestinal toxicity in the validation cohort. When the two cohorts were combined, XPC rs2228000 presented better tolerance of severe hematologic toxicity, gastrointestinal toxicity and leukopenia (OR=0.677, 95% CI: 0.510-0.899, P=0.007; OR=0.565, 95% CI: 0.368-0.869, P=0.009; and OR=0.628, 95% CI: 0.439-0.899, P=0.011, respectively). Our findings can offer comprehensive pharmacogenetic information for platinum-induced toxicities. This article is protected by copyright. All rights reserved.

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Birth rates after radioactive iodine treatment for differentiated thyroid cancer

Abstract

Treatment with radioactive iodine (RAI) for differentiated thyroid cancer has been associated with alterations in gonadal function in women, including changes in menstrual function and an earlier age at menopause. Our objective was to evaluate associations between RAI and post-diagnosis live birth rates among thyroid cancer survivors diagnosed at ages 15-39 years. We identified women diagnosed with differentiated thyroid cancer between January 2000 and December 2013 in the North Carolina Central Cancer Registry (CCR). CCR records were linked to state birth certificate files to identify livebirths to thyroid cancer survivors through December 2014. Person-years of follow-up were accrued from 6 months after diagnosis to first birth, 46^th birthday, death, or December 31, 2014, whichever came first. Cox proportional hazards regression was used to estimate hazards ratios (HR) and 95% confidence intervals (CI) for first livebirth. Among 2,360 women with a differentiated thyroid cancer diagnosis, 53% received RAI. The cumulative incidence of birth at the end of follow-up (maximum 14.5 years) was 30.0% and 29.3% among those who were and were not treated with RAI, respectively. Overall, first birth rates did not significantly differ between groups (HR=1.00; 95% CI: 0.82, 1.23). In our observational cohort, treatment with RAI was not associated with a reduced birth rate. Our findings add to the evidence available for counseling thyroid cancer patients with concerns about future fertility. This article is protected by copyright. All rights reserved.

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Bilateral medial rectus aplasia and a modified surgical approach of transposition myopexy of vertical recti

A 16-year-old girl presented with left eye large-angle exotropia. On examination, we found bilateral limitation of adduction. CT orbit showed hypoplastic medial rectus bilaterally, but intraoperatively we found absent medial recti on both sides. This case report explains discrepancy between the imaging and the intraoperative findings and discusses the management dilemma in view of the risk of anterior segment ischaemia and how marked exodeviation and adduction limitation was tackled by the new technique of transposition myopexy, a modification of the procedure described by Nishida along with recession of lateral rectus to achieve good alignment. This procedure changes the vector forces of the vertical rectus without splitting or tenotomy of the muscles.

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Euglycaemic ketoacidosis: a potential new hazard to plastic surgery day case and inpatient procedures

A woman aged 44 underwent elective standard abdominoplasty and bilateral mastopexy (superiorly based pedicle with vertical scar) following weight loss of 8.5 stone (53.9 kg) over a 5-year period. She had type 2 diabetes and her antidiabetic medications included metformin, liraglutide and empagliflozin. Towards the end of the first postoperative day, she reported gradual onset of nausea, vomiting and abdominal pain. Her condition continued to deteriorate overnight, becoming tachycardic and tachypnoeic. Urgent investigations showed severe diabetic ketoacidosis with euglycaemia. She was managed with fluid resuscitation, insulin infusion and intravenous sodium bicarbonate in the high dependency unit. She made a complete clinical and biochemical recovery and was discharged on day 9 postoperatively. This case illustrates a diagnostic challenge of a serious life-threatening complication of diabetes in the postoperative period associated with a novel class of antidiabetic medications, sodium-glucose cotransporter 2 inhibitors.

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A rare cause of early neonatal cyanosis: absent right pulmonary artery

Unilateral absent right pulmonary artery is a rare developmental anomaly that usually presents in late childhood and adolescence as recurrent respiratory tract infections, dyspnoea and haemoptysis. We report a case of a 2-day-old baby with respiratory distress and differential cyanosis. Echocardiogram showed pulmonary hypertension with absent right pulmonary artery. The findings were confirmed by CT angiogram. The baby improved with pulmonary vasodilators and antifailure medications.

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Ventilator respiratory graphic diagnosis of hiccupping in non-ketotic hyperglycinaemia

A neonate presented with early encephalopathy deteriorated and was intubated and ventilated. Ventilator data were monitored and recorded at 100 Hz for 24 hours.

The infant had many sudden deep inspirations during this time which were initially thought to be seizures. These were characterised by short, rapid, large inspirations when the airway pressure was reduced well below the positive end expiratory pressure level. Analysis of the ventilator data showed that these were hiccupping episodes misinterpreted by the ventilator as spontaneous breaths and triggering ventilator inflations. The expired tidal volumes during the hiccupping episodes were more than double the set 4.5 mL/kg. During these episodes, there was no change in the level of consciousness or in the amplitude-integrated electroencephalogram signal. Detailed respiratory recording of pathological hiccups has not been reported.

Metabolic screening diagnosed non-ketotic hyperglycinaemia. Hiccups commonly occur in this condition and should not be misinterpreted as seizures, spontaneous breaths or gasps.

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When a black olive kernel causes SBO: first comparison of CT acquisition

Description

A man aged 24 years presented with acute abdominal pain since 2 days. His past medical history was unremarkable. On physical examination, the abdomen was tender, soft and tympanic to percussion, with absent bowel sounds. CT of the abdomen revealed imaging signs indicating mechanical small bowel obstruction (SBO) related to ileal wall thickening (figure 1A) and to the presence of an alimentary fragment (an olive with its stone, one of the favourite foods of the patient) (figure 1A). The nature of the foreign body causing the SBO was suspected by the detailed history taking of the patient's alimentary habits. To confirm this diagnosis, a CT acquisition (figure 1B) of fresh olives (figure 1C) was made and the picture was compared with the patient images.

Figure 1

(A) Pelvic small bowel dilated loop with an ileal wall thickening...

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Optic disc swelling in a patient with tuberculous meningitis: a diagnostic challenge

We discuss the diagnostic challenge in an adult patient presented with purely ocular symptoms diagnosed with tuberculous meningitis (TBM). A 38-year-old woman presented with bilateral painless blurring of vision. There were bilateral sixth cranial nerve palsy and bilateral optic disc swelling. Optic nerve function tests were normal. Patient was lucid with no signs of meningism. Brain imaging were normal. She had a positive Mantoux test, high erythrocyte sedimentation rate but no clinical evidence of active pulmonary tuberculosis infection. Her Quantiferon-TB Gold in-tube test was negative. Cerebrospinal fluid analysis revealed a high opening pressure but no biochemical parameters to suggest TBM, hence she was treated as idiopathic intracranial hypertension. A diagnosis of TBM was finally made following a positive PCR for Mycobacterium tuberculosis. Her vision improved with reduction in optic disc swelling following antituberculous treatment.

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Discerning the optic nerve and retinochoroidal pathology using B-scan ultrasound in cases with anterior segment opacity

Description

Case 1: A posterior segment B-scan ultrasonography in a patient with typical iris coloboma and total cataract, showed well-defined excavated area in the inferior part just below the optic disc (red arrow) with the absence of retinochoroidal layer, suggestive of fundal coloboma (yellow arrow) (figure 1A). Involvement of macula and types of fundal coloboma can be ascertained quite fairly based on ultrasonography which might provide a clue or prediction about postoperative visual gain or visual prognosis.1

Figure 1

(A) Axial scan depicting a well-defined posterior ocular coat excavation below the optic nerve head (red arrow) is suggestive of fundal coloboma (yellow arrow). (B) Axial scan showing a well-defined excavated area over the optic nerve head (red arrow) suggests an optic disc coloboma (yellow arrow) along with thinned out inferior neuroretinal rim (purple arrow). (C) Axial scan revealed an uniform diffuse...

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