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Advances in cancer treatment have led to improved survival but have also increased morbidity and mortality due to direct side-effects of the treatment on cardiovascular function. This document reviews the different steps in cardiovascular monitoring and decision-making before during and after cancer treatment with potential cardiovascular side-effects.

Taste acuity of adult patients undergoing cancer treatment has been well investigated; however, studies of taste acuity after completion of cancer treatment are limited, particularly in children. This study aimed to assess taste acuity in pediatric cancer patients after treatment completion. Seventy-three patients who had completed cancer treatment (median age, 13 years; range, 7 - 18 years) and had not received any further treatment for at least 6 months were enrolled. Eighty-one healthy children (median age, 10 years; range, 8 - 19 years) served as controls. We determined the thresholds for four tastes (sweet, salty, sour, and bitter) using the filter-paper disc method. There was no significant difference in the thresholds of taste acuity for the four test solutions between the patient and control groups. The duration since treatment completion (

In this month’s editorial, the PLOS Medicine Editors announce an upcoming Special Issue, with Guest Editors Elaine Mardis and Marc Ladanyi, on actionable advances in research on the cancer genome.

Nicola Low and colleagues announce a call for research papers on sexually transmitted infections, to accompany a Collection on the topic.

It is widely accepted that cancer patients have unmet psychosocial needs. There are as yet few guidelines on the appropriate role of a counsellor in centres for cancer treatment. In this study the activities of a radiographer counsellor were audited to try to identify the proportion of patients who would benefit from seeing a counsellor, to estimate the cost of such a service, and to obtain indications of how the effects of counselling could be evaluated. The study suggested that 44% of patients attending for routine radiotherapy have abnormally high levels of anxiety and might benefit from counselling. The Hospital Anxiety and Depression Scale (HADS) is proposed as an objective measure of benefit. Costing and resource allocation are discussed.

Aims to investigate the causative factors and clinical applicability of spontaneous regression of malignant tumours without treatment, a really paradoxical phenomenon with many therapeutic potentialities. Analyses past cases to find that the commonest cause is a preceding episode of high fever‐induced thermal fluctuation which produces fluctuation of biochemical/immunological parameters. Using Prigogine‐Glansdorff‐Langevin stability theory and biocybernetic principles, develops the theoretical foundation of a tumour’s self‐control, homeostasis and regression induced by thermal, radiation or oxygenation fluctuations. Derives a threshold condition of perturbations for producing regression. Presents some striking confirmation of such fluctuation‐induced regression in Ewing tumour, Clear cell cancer and Lewis lung carcinoma. Using experimental data on patients, elucidates a novel therapeutic approach of multi‐modal hyper‐fluctuation utilizing radiotherapeutic hyper‐fractionation, temperature and immune‐status.

Introduction Patients with cancer undergoing active systemic anticancer treatment (chemotherapy, immunotherapy, targeted, or combination therapy) are at greater risk of COVID-19 infection than persons without cancer. In this paper, the authors analyse the spread of the coronavirus among cancer patients undergoing systemic therapy, and the impact of COVID-19 infection on the continuation of cancer treatment and its outcome at one community hospital in a mid-sized city in the south of Poland. Material and methods Nasopharyngeal swab was the only collection method used to obtain specimens for testing via real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Only those with positive RT-PCR results were considered as confirmed SARS-CoV-2 cases. We analysed the medical records of patients quarantined in a hospital clinical oncology ward due to confirmed COVID-19 infection in one member of the group. Qualitative measures are presented as the percentage of their occurrence, and these were evaluated with Fisher’s test. Differences were considered significant at p < 0.05. Results Cancer patients had more frequent confirmed COVID-19 infection than other patients (3.7% vs. 1.2%). Among cancer patients COVID-19 infection was significantly more frequent in women than in men, p = 0.005. The fatality rate was 27.3% in cancer patients undergoing active anticancer therapy, compared to 3% in the general Polish population. Neither heparin nor G-CSF use had any influence on COVID-19 infection. Conclusions In this analysis, the only significant negative factor for COVID-19 infection was female sex, RR (95% CI) = 4.5 (1.3–15.8), (p = 0.005), and this was attributable to individual behaviour.

Though promising, identifying synergistic combinations from a large pool of candidate drugs remains challenging for cancer treatment. Due to unclear mechanism and limited confirmed cases, only a few computational algorithms are able to predict drug synergy. Yet they normally require the drug-cell treatment results as an essential input, thus exclude the possibility to pre-screen those unexplored drugs without cell treatment profiling. Based on the largest dataset of 33,574 combinational scenarios, we proposed a handy webserver, H-RACS, to overcome the above problems. Being loaded with chemical structures and target information, H-RACS can recommend potential synergistic pairs between candidate drugs on 928 cell lines of 24 prevalent cancer types. A high model performance was achieved with AUC of 0.89 on independent combinational scenarios. On the second independent validation of DREAM dataset, H-RACS obtained precision of 67% among its top 5% ranking list. When being tested on new combinations and new cell lines, H-RACS showed strong extendibility with AUC of 0.84 and 0.81 respectively. As the first online server freely accessible at http://www.badd-cao.net/h-racs, H-RACS may promote the pre-screening of synergistic combinations for new chemical drugs on unexplored cancers.

Background: With the anti-cancer efficacies of cold atmospheric plasma being increasingly recognized in vitro, a demand on creating an effective tool feasible for in vivo animal treatment has emerged. Methods: Through the use of co-axial needles with different calibers in diameter, we designed a novel in situ ejection source of cold atmospheric plasma, namely invivoPen, for animal experiments. It punches just a single pinhole that could considerably ease the complexity of operating with small animals such as mouse. Results: We showed that invivoPen could deliver similar efficacies as plasma activated medium with reduced cost in suppressing cell proliferation and migration as well as potentially boosting the viabilities of mice receiving invivoPen treatment. Blood test, renal and liver functionalities tests all suggest that physical plasma could effectively return tumor-carrying mice to the healthy state without harm to body conditions, and invivoPen slightly outweighs PAM in boosting animal immunity and reducing inflammation. Conclusion: Our study contributes to the community in providing a minimal invasive in situ plasma source, having partly explained the efficacies of cold atmospheric plasma in treating triple negative breast cancers, and proposing the potential synergies between physical plasma and conventional drugs for cancer treatment.

Methyltransferase-like 1 (METTL1) mediated 7-methylguanosine (m7G) is crucial for the regulation of chemoresistance in cancer treatment. However, the role of METTL1 in regulating chemoresistance of colon cancer (CC) cells to cisplatin is still unclear. This study established the cisplatin-resistant CC (CR-CC) cells and found that METTL1 was low-expressed in CR-CC cells compared to their paired cisplatin-sensitive CC (CS-CC) cells. Besides, overexpressed METTL1 enhanced the cytotoxic effects of cisplatin on CR-CC cells. In addition, miR-149-3p was the downstream target of METTL1, which could be positively regulated by METTL1. Further results validated that miR-149-3p was low-expressed in CR-CC cells comparing to the CS-CC cells. In addition, the promoting effects of overexpressed METTL1 on cisplatin induced CR-CC cell death were abrogated by synergistically knocking down miR-149-3p. Furthermore, S100A4/p53 axis was the downstream target of METTL1 and miR-149-3p, and either overexpressed METTL1 or miR-149-3p increased p53 protein levels in CR-CC cells, which were reversed by upregulating S100A4. Similarly, the promoting effects of overexpressed METTL1 on cisplatin-induced CR-CC cell death were abrogated by overexpressing S100A4. Taken together, overexpression of METTL1 sensitized CR-CC cells to cisplatin by modulating miR-149-3p/S100A4/p53 axis.

Galunisertib (Gal) is a transforming growth factor (TGF-β) blockade which is being investigated as a potential tumor immunotherapy candidate drug in clinical trials. However, primary or acquired resistance is often found in the recruited cancer patients, which limits its clinical application. Tumor immune microenvironment can be regulated by intestinal microbiota, leading to different therapeutic outcomes. It is hypothesized that manipulation of cancer patients' intestinal microbiome in the early stage of therapy may be a promising strategy to improve the therapeutic efficacy of Gal. Methods: 4T1 and H22 subcutaneous tumor bearing mice were used to evaluate the therapeutic effect. Escherichia coli strain Nissle 1917 (EcN), a widely used probiotic bacteria, was orally delivered to the tumor bearing mice daily along with Gal treatment. Antitumor effect of the combination therapy was evaluated by tumor volume, histological staining of tumor tissues. Furthermore, flow cytometry was performed to analyze the alteration of immune microenvironment in tumor bed after treatment. The suppressing effect of the combination therapy on tumor invasiveness and metastasis was evaluated in both mice and zebrafish xenografts models. Fecal sample 16S rRNA gene sequencing was conducted to analyze changes of intestinal microbial diversity. The effect of intestinal microbiota on tumor suppression after receiving EcN was further tested by fecal transplant. Results: The therapeutic outcomes in tumor growth inhibition and metastasis suppression of Gal were significantly potentiated by EcN, resulting from the strengthened antitumor immunity. EcN was able to relieve the immunosuppressive tumor microenvironment, which was evidenced by enhanced tumor-specific effector T cells infiltration and dendritic cells activation. Intestinal microbiota was modulated by EcN, illustrated by a shift of gut microbiome toward certain beneficial bacteria. Conclusion: These results suggested that Gal combined with EcN might be a novel therapeutic approach with great potential of clinical implications for cancer prevention or treatment.

Significance: Terahertz (THz) radiation has demonstrated a great potential in biomedical applications over the past three decades, mainly due to its non-invasive and label-free nature. Among all biological specimens, skin tissue is an optimal sample for the application of THz-based methods because it allows for overcoming some intrinsic limitations of the technique, such as a small penetration depth (0.1 to 0.3 mm for the skin, on average). Aim: We summarize the modern research results achieved when THz technology was applied to the skin, considering applications in both imaging/detection and treatment/modulation of the skin constituents. Approach: We perform a review of literature and analyze the recent research achievements in THz applications for skin diagnosis and investigation. Results: The reviewed results demonstrate the possibilities of THz spectroscopy and imaging, both pulsed and continuous, for diagnosis of skin melanoma and non-melanoma cancer, dysplasia, scars, and diabetic condition, mainly based on the analysis of THz optical properties. The possibility of modulating cell activity and treatment of various diseases by THz-wave exposure is shown as well. Conclusions: The rapid development of THz technologies and the obtained research results for skin tissue highlight the potential of THz waves as a research and therapeutic instrument. The perspectives on the use of THz radiation are related to both non-invasive diagnostics and stimulation and control of different processes in a living skin tissue for regeneration and cancer treatment.

It is important that patient-reported outcome (PRO) measures used to assess cancer therapies adequately capture the benefits and risks experienced by patients, particularly when adverse event profiles differ across therapies. This study explores the case for augmenting preference-based utility measures to capture the impact of cancer treatment-related symptoms. Additional cancer treatment-related items could be specific (e.g., rash) or global. While specific items are easier to describe and understand, their use may miss rarer symptoms and those that are currently unknown but will arise from future medical advancements. The appropriate number of additional items, the independence of those items, and their impact on the psychometric properties of the core instrument require consideration. Alternatively, a global item could encompass all potential treatment-related symptoms, of any treatments for any disease. However, such an item may not be well understood by general public respondents in valuation exercises. Further challenges include the decision about whether to generate de novo value sets for the modified instrument or to map to existing tariffs. The fluctuating and transient nature of treatment-related symptoms may be inconsistent with the methods used in conventional valuation exercises. Fluctuating symptoms could be missed by sub-optimal measure administration timing. The addition of items also poses double-counting risks. In summary, the addition of treatment-related symptom items could increase the sensitivity of existing utility measures to capture known and unknown treatment effects in oncology, while retaining the core domains. However, more research is needed to investigate the challenges, particularly regarding valuation.

// Costi Alifrangis 1 , Philip Carter 2 , Biancastella Cereser 2 , Pramodh Chandrasinghe 2, 3 , Lisa Del Bel Belluz 2 , Eric Lim 4 , Nina Moderau 2 , Fotini Poyia 2 , Neha Tabassum 2 , Hua Zhang 5 , Jonathan Krell 2 and Justin Stebbing 2 1 Department of Oncology, University College Hospital, London, UK 2 Department of Surgery and Cancer, Imperial College, London, UK 3 Department of Surgery, University of Kelaniya, Kelaniya, Sri Lanka 4 National Heart and Lung Institute, Imperial College, London, UK 5 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Correspondence to: Philip Carter, email: phil.carter@imperial.ac.uk Keywords: tumor profiling; lung cancer; NSCLC; non-small cell lung cancer; cancer treatment Abbreviations: 5FU: fluorouracil; IHC: immunohistochemistry; NSCLC: non-small cell lung cancer; OS: overall survival Received: July 29, 2017 Accepted: January 01, 2018 Published: February 01, 2018 ABSTRACT In this study we utilized data on patient responses to guided treatments, and we evaluated their benefit for a non-small cell lung cancer cohort. The recommended therapies used were predicted using tumor molecular profiles that involved a range of biomarkers but primarily used immunohistochemistry markers. A dataset describing 91 lung non-small cell lung cancer patients was retrospectively split into two. The first group’s drugs were consistent with a treatment plan whereby all drugs received agreed with their tumor’s molecular profile. The second group each received one or more drug that was expected to lack benefit. We found that there was no significant difference in overall survival or mortality between the two groups. Patients whose treatments were predicted to be of benefit survived for an average of 402 days, compared to 382 days for those that did not ( P = 0.7934). In the matched treatment group, 48% of patients were deceased by the time monitoring had finished compared to 53% in the unmatched group ( P = 0.6094). The immunohistochemistry biomarker for the ERCC1 receptor was found to be a marker that could be used to predict future survival; ERCC1 loss was found to be predictive of poor survival.

Physically precise external-beam radiotherapy (EBRT) technologies may not translate to the best outcome in individual patients. On the other hand, clinical considerations alone are often insufficient to guide the selection of a specific EBRT approach in patients. We examine the ways in which to compare different EBRT approaches based on physical, biological and clinical considerations, and how they can be enhanced with the addition of biophysical models and machine-learning strategies. The process of selecting an EBRT modality is expected to improve in tandem with knowledge-based treatment planning.

Background Oncology has been facing increasing outpatient activity associated with higher cancer incidence, better survival rates, and more treatment options. Innovative technological solutions could help deal with this increasing demand. Using digital patient-reported outcome measures (PROMs) to identify patients who need a face-to-face (FTF) appointment is a potential approach. Objective This study aims to assess the feasibility of digital PROM questionnaires to enable remote symptom monitoring for patients undergoing cancer treatment and their ability to highlight the requirement for an FTF appointment. Methods This study was performed at a tertiary oncology center between December 2018 and February 2019. The Common Terminology Criteria for Adverse Events were adapted into patient-friendly language to form the basis of treatment-specific digital questionnaires covering specific cancer drugs and radiotherapy treatments. These treatment-specific digital PROM questionnaires were scored by both patients and their clinicians during FTF appointments. Patients and clinicians did not see each other’s scored PROMs. Agreement between patients and clinicians was assessed using descriptive statistics. Patient and staff feedback was also obtained. Results In total, 90 patients participated in the study across 10 different treatment pathways. By comparing paired patient and clinician responses, the sensitivity of the patient-completed questionnaires in correctly highlighting the need for FTF review was 94% (44/47), and all patients with severe or grade 3+ symptoms were identified (6/6, 100%). Patient-completed PROMs appropriately revealed that 29% (26/90) of the participating patients did not need FTF review based on their symptoms alone. Certain oncological treatment pathways, such as immunotherapy, were found to have a larger proportion of patients with minimal symptoms than others, such as conventional chemotherapy. Patient and staff feedback showed high approval of digital PROMs and their potential for use in remote monitoring. Conclusions Digital PROM questionnaires can feasibly highlight the need for FTF review in oncology clinics for treatment. Their use with specific treatments could safely reduce the requirement for FTF care, and future work should evaluate their application in the remote monitoring of patients.

Background The COVID-19 pandemic has disrupted cancer services globally. New Zealand has pursued an elimination strategy to COVID-19, reducing (but not eliminating) this disruption. Early in the pandemic, our national Cancer Control Agency (Te Aho o Te Kahu) began monitoring and reporting on service access to inform national and regional decision-making. In this manuscript we use high-quality, national-level data to describe changes in cancer registrations, diagnosis and treatment over the course of New Zealand's response to COVID-19. Methods Data were sourced (2018–2020) from national collections, including cancer registrations, inpatient hospitalisations and outpatient events. Cancer registrations, diagnostic testing (gastrointestinal endoscopy), surgery (colorectal, lung and prostate surgeries), medical oncology access (first specialist appointments [FSAs] and intravenous chemotherapy attendances) and radiation oncology access (FSAs and megavoltage attendances) were extracted. Descriptive analyses of count data were performed, stratified by ethnicity (Indigenous Māori, Pacific Island, non-Māori/non-Pacific). Findings Compared to 2018–2019, there was a 40% decline in cancer registrations during New Zealand's national shutdown in March-April 2020, increasing back to pre-shutdown levels over subsequent months. While there was a sharp decline in endoscopies, pre-shutdown volumes were achieved again by August. The impact on cancer surgery and medical oncology has been minimal, but there has been an 8% year-to-date decrease in radiation therapy attendances. With the exception of lung cancer, there is no evidence that existing inequities in service access between ethnic groups have been exacerbated by COVID-19. Interpretation The impact of COVID-19 on cancer care in New Zealand has been largely mitigated. The New Zealand experience may provide other agencies or organisations with a sense of the impact of the COVID-19 pandemic on cancer services within a country that has actively pursued elimination of COVID-19. Funding Data were provided by New Zealand's Ministry of Health, and analyses completed by Te Aho o Te Kahu staff.

Immunotherapy has brought high hopes for cancer treatment, and attracted tremendous resources from the biopharmaceutical community. Here we analyze cancer immunotherapy-related patents granted by the United States Patent and Trademark Office in the past decade (2006-2016). A total of 2,229 patents were identified in 13 subfields. The growth of patent number in this field has outpaced the background rate, with cytokine-related therapies, immune checkpoint inhibitors, and natural killer cell therapies growing the most rapidly. The top 15 assignees possess 27.6% (616) of the patents. Amgen is the largest patent holder, followed by Novartis, and then by Chugai Seiyaku. The top assignees have focused on different subfields, and collaborated with each other for technology development. Our competitive analysis reveals that Novartis, Chugai Seiyaku, and Abbvie lead in both patent number and average quality of patents. Meanwhile, Immunomedics owns a high-quality though relatively small patent portfolio in single-chain variable fragment technology, which is not the focus of the abovementioned forerunners. Overall, our analysis illustrates an ecosystem where industry giants and smaller-size players each occupies a niche. Selection and succession are expected to continue for years in this young ecosystem.

// Paola de Andrade Mello 1, 2, * , Shu Bian 2, 3, * , Luiz Eduardo Baggio Savio 2, 4 , Haohai Zhang 2, 5 , Jingping Zhang 6 , Wolfgang Junger 6 , Marcia Rosângela Wink 7 , Guido Lenz 8 , Andreia Buffon 1 , Yan Wu 2, ** and Simon Christopher Robson 2, ** 1 Laboratorio de Analises Bioquimicas e Citologicas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil 2 Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Harvard University, Boston, MA, USA 3 Department of Gastroenterology, Tianjin Union Medical Center, Tianjin, P.R. China 4 Programa de Imunobiologia, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil 5 Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China 6 Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Harvard University, Boston, MA, USA 7 Laboratorio de Biologia Celular, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil 8 Departamento de Biofisica e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil * Co-first author ** Joint senior authors Correspondence to: Simon Christopher Robson, email: srobson@bidmc.harvard.edu Yan Wu, email: ywu@bidmc.harvard.edu Keywords: purinergic signaling, hyperthermia, membrane fluidity, cancer therapy, colon cancer Received: February 22, 2017 Accepted: May 22, 2017 Published: June 21, 2017 ABSTRACT Extracellular ATP (eATP) accumulation within the tumor microenvironment (TME) has the potential to activate purinergic signaling. The eATP evoked signaling effects bolster antitumor immune responses while exerting direct cytotoxicity on tumor cells and vascular endothelial cells, mediated at least in part through P2X7 receptors. Approaches to augment purinergic signaling in TME e.g. by ectonucleotidase CD39 blockade, and/or boosting P2X7 functional responses, might be used as immunomodulatory therapies in cancer treatment. In this study, we delineated the translatable strategy of hyperthermia to demonstrate impacts on P2X7 responsiveness to eATP. Hyperthermia (40°C) was noted to enhance eATP-mediated cytotoxicity on MCA38 colon cancer cells. Increased membrane fluidity induced by hyperthermia boosted P2X7 functionality, potentiating pore opening and modulating downstream AKT/PRAS40/mTOR signaling events. When combined with cisplatin or mitomycin C, hyperthermia and eATP together markedly potentiate cancer cell death. Our data indicate that clinically tolerable hyperthermia with modulated P2X7-purinergic signaling will boost efficacy of conventional cancer treatments.

Although previous decades contributed to major progress in targeted therapy of many malignancies, the treatment of gynaecological cancers remains a challenging task. In the evidence of rising cancer mortality, the search for new methods of treatment is a dire need. Exploring the mechanisms of interaction between tumour cells and host immune response may allow the introduction of new, effective therapies – not as toxic and far more efficient than conventional methods of cancer treatment. Epithelial ovarian cancer (EOC) is typically diagnosed at advanced stages. Its incidence and mortality rate is high. Powerful diagnostic tools for this kind of cancer are still under investigation. Multiple mechanisms existing in the ovarian tumour network create a specific immunosuppressive microenvironment, in which accumulation of myeloid-derived suppressor cells (MDSCs) may be a critical component for diagnosis and treatment. This review attempts to verify current knowledge on the role of MDSCs in EOC.

Cancer incidence and mortality depend on a number of factors, including age, socio-economic status and geographical location, and its prevalence is growing around the world. Most of cancer treatments include external beam radiotherapy or brachytherapy. Brachytherapy, a type of radiotherapy with energy from radionuclides inserted directly into the tumor, is increasingly used in cancer treatment. For cervical and skin cancers, it has become a standard therapy for more than 100 years as well as an important part of the treatment guidelines for other malignancies, including head and neck, skin, breast, and prostate cancers. Compared to external beam radiotherapy, brachytherapy has the potential to deliver an ablative radiation dose over a short period of time directly to the altered tissue area with the advantage of a rapid fall-off in dose, and consequently, sparing of adjacent organs. As a result, the patient is able to complete the treatment earlier, and the risks of occurrence of another cancer are lower than in conventional radiotherapy treatment. Brachytherapy has increased its use as a radical or palliative treatment, and become more advanced with the spread of pulsed-dose-rate and high-dose-rate afterloading machines; the use of new 3D/4D planning systems has additionally improved the quality of the treatment. The aim of the present study was to present short summaries of current studies on brachytherapy for the most frequently diagnosed tumors. Data presented in this manuscript should help especially young physicians or physicists to explore and introduce brachytherapy in cancer treatments.

// Sissel Hauge 1 , Christian Naucke 1 , Grete Hasvold 1 , Mrinal Joel 1 , Gro Elise Rodland 1 , Petras Juzenas 1 , Trond Stokke 1 , Randi G. Syljuasen 1 1 Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, N-0310, Norway Correspondence to: Randi G. Syljuasen, email: randi.syljuasen@rr-research.no Keywords: checkpoint kinase inhibitors, cancer treatment, replication stress, DNA damage, CDK activity Received: August 04, 2016 Accepted: December 15, 2016 Published: December 22, 2016 ABSTRACT Recent studies have shown synergistic cytotoxic effects of simultaneous Chk1- and Wee1-inhibition. However, the mechanisms behind this synergy are not known. Here, we present a flow cytometry-based screen for compounds that cause increased DNA damage in S-phase when combined with the Wee1-inhibitor MK1775. Strikingly, the Chk1-inhibitors AZD7762 and LY2603618 were among the top candidate hits of 1664 tested compounds, suggesting that the synergistic cytotoxic effects are due to increased S-phase DNA damage. Combined Wee1- and Chk1-inhibition caused a strong synergy in induction of S-phase DNA damage and reduction of clonogenic survival. To address the underlying mechanisms, we developed a novel assay measuring CDK-dependent phosphorylations in single S-phase cells. Surprisingly, while Wee1-inhibition alone induced less DNA damage compared to Chk1-inhibition, Wee1-inhibition caused a bigger increase in S-phase CDK-activity. However, the loading of replication initiation factor CDC45 was more increased after Chk1- than Wee1-inhibition and further increased by the combined treatment, and thus correlated well with DNA damage. Therefore, when Wee1 alone is inhibited, Chk1 suppresses CDC45 loading and thereby limits the extent of unscheduled replication initiation and subsequent S-phase DNA damage, despite very high CDK-activity. These results can explain why combined treatment with Wee1- and Chk1-inhibitors gives synergistic anti-cancer effects.

BackgroundA reproductive health implication of the increasing incidence of cancer among women is the impact of cancer treatment on fertility.ObjectiveAs patients are increasingly using the internet, particularly online forums, to seek and share experiences, our objective was to understand information needs about cancer treatment, fertility, and pregnancy of women with cancer as well as their caregivers.MethodsWe searched threads (original posts and responses) on four subreddit sites of Reddit (“r/Cancer,” “r/TryingForABaby,” “r/BabyBumps,” and “r/Infertility”) over a 5‐year period between February 4th, 2014 and February 4th, 2019. Threads with original posts involving a lived experience or question regarding cancer treatment and female fertility and/or pregnancy or parenting/having children from the perspective of either patient or caregiver were included in our analysis. We analyzed threads using thematic analysis.ResultsFrom 963 Reddit threads identified, 69 were analyzed, including 56 with original posts by women with cancer and 13 with original posts by caregivers. From threads made by patients, we identified themes on becoming a part of an online community, impacts of cancer treatment and fertility concerns on self and social relationships, making family planning decisions, and experiences with medical team. We also identified a theme on the impact of cancer treatment and fertility concerns on caregivers.ConclusionsReddit provided a rich pool of data for analyzing the information needs of women facing cancer. Our findings demonstrate the far-reaching impacts of cancer treatment and fertility on physical, mental, and psychosocial health for both patients and their caregivers.

Motivation: Combinatorial therapies have been under intensive research for cancer treatment. However, due to the large number of possible combinations among candidate compounds, exhaustive screening is prohibitive. Hence, it is important to develop computational tools that can predict compound combination effects, prioritize combinations and limit the search space to facilitate and accelerate the development of combinatorial therapies. Results: In this manuscript we consider the NCI-DREAM Drug Synergy Prediction Challenge dataset to identify features informative about combination effects. Through systematic exploration of differential expression profiles after single compound treatments and comparison of molecular structures of compounds, we found that synergistic levels of combinations are statistically significantly associated with compounds’ dissimilarity in structure and similarity in induced gene expression changes. These two types of features offer complementary information in predicting experimentally measured combination effects of compound pairs. Our findings offer insights on the mechanisms underlying different combination effects and may help prioritize promising combinations in the very large search space. Availability and Implementation: The R code for the analysis is available on https://github.com/YiyiLiu1/DrugCombination. Contact: hongyu.zhao@yale.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein we compare two NIR-light sources; light emitting diodes (LEDs) and Lasers, for their effectiveness in NIR-PIT. A photosensitizer, IRDye-700DX, conjugated to panitumumab (pan-IR700), was incubated with EGFR-expressing A431 and MDA-MB-468-luc cells. NIR-light was provided by LEDs or Lasers at the same light dose. Laser-light produced more cytotoxicity and greater reductions in IR700-fluorescence intensity than LED-light. Laser-light also produced more cytotoxicity in vivo in both cell lines. Assessment of super-enhanced permeability and retention (SUPR) effects were stronger with Laser than LED. These results suggest that Laser-light produced significantly more cytotoxic effects compared to LEDs. Although LED is less expensive, Laser-light produces superior results in NIR-PIT.

This study investigated a remote symptom monitoring intervention to examine if older participants with cancer received a similar magnitude of benefit compared with younger adults with cancer. We analyzed a longitudinal symptom monitoring intervention for 358 participants beginning a new course of chemotherapy treatment in community and academic oncology practices. The study design was a randomized control trial; participants were randomized to the intervention or usual care, the intervention was delivered during daily automated coaching. Older adults with moderate and severe symptoms derived similar benefit as those adults younger than 60 years of age, adherence to the study protocol which involved daily calls was high. There was no significant difference between the 2 age categories; on average, older adult participants made 88% of expected daily calls and younger adult participants made 90% of expected daily calls. Our results challenge the perception that older adults are unwilling or unable to use a technological tool such as interactive voice response and suggest that patient utilization may be guided by other factors, such as ease of use and perceived benefit from the intervention.

Solid tumors are typically supplied nutrients by a network of irregular blood vessels. By targeting these vascular networks, it might be possible to hinder cancer growth and metastasis. Vascular disrupting agents induce intertumoral hemorrhaging, making photoacoustic (PA) imaging well positioned to detect bleeding due to its sensitivity to hemoglobin and its various states. We introduce a fractal-based numerical model of intertumoral hemorrhaging to simulate the PA signals from disrupted tumor blood vessels. The fractal model uses bifurcated cylinders to represent vascular trees. To mimic bleeding from blood vessels, hemoglobin diffusion from microvessels was simulated. In the simulations, the PA signals were detected by a linear array transducer (30 MHz center frequency) of four different vascular trees. The power spectrum of each beamformed PA signal was computed and fitted to a straight line within the −6-dB bandwidth of the receiving transducer. The spectral slope and midband fit (MBF) based on the fit decreased by 0.11 dB / MHz and 2.12 dB, respectively, 1 h post bleeding, while the y-intercept increased by 1.21 dB. The results suggest that spectral PA analysis can be used to measure changes in the concentration and spatial distribution of hemoglobin in tissue without the need to resolve individual vessels. The simulations support the feasibility of using PA imaging and spectral analysis in cancer treatment monitoring by detecting microvessel disruption.

Next-generation sequencing has produced a large quantity of DNA or RNA sequences related to the processes occurring within tumors and their microenvironment in a reasonable time and cost. These data have been used to guide the identification of neoantigens and to determine their specific T-cell receptors. Furthermore, adoptive T-cell therapy targeting neoantigens is under development for cancer treatment. In this review, we first provide an overview of sequencing technologies and the updated findings concerning neoantigens related to adoptive T-cell therapy and then summarize the methods and principles underlying the development of next-generation sequencing-based neoantigen-reactive T-cell therapy for cancer.

Immunotherapies have revolutionized cancer treatment. Immunotherapy is effective for the treatment of a wide range of cancer types and can mediate complete and durable tumor regression. Nonetheless, the field still faces many significant challenges, such as the need for personalized therapeutic strategies and better biomarkers, the difficulty of selecting the right combination therapy, and resistance to currently available immunotherapies. Both cancer and host immunity comprise significantly diverse and complex ecosystems, making immunogenomics an ideal field for functional genomics analysis. In this review, we describe the cancer-immunity cycle, how cancer cells manage to evade immune attack and the current hurdles in the path of cancer immunotherapy. Then, we discuss how functional genomics approaches can pave the way for more successful cancer immunotherapies.

// Naoki Fukuda 1 , Daisuke Takahari 1 , Takeru Wakatsuki 1 , Hiroki Osumi 1 , Izuma Nakayama 1 , Tomohiro Matsushima 1 , Takashi Ichimura 1 , Mariko Ogura 1 , Masato Ozaka 1 , Mitsukuni Suenaga 1 , Eiji Shinozaki 1 , Keisho Chin 1 and Kensei Yamaguchi 1 1 Department of Gastroenterology, The Cancer Institute Hospital of JFCR, Tokyo, Japan Correspondence to: Daisuke Takahari, email: daisuke.takahari@jfcr.or.jp Keywords: ramucirumab; gastric cancer; hypertension; paclitaxel; toxicity Received: December 04, 2017 Accepted: February 25, 2018 Epub: March 08, 2018 Published: March 16, 2018 ABSTRACT Anti-vascular endothelial growth factor (VEGF) therapeutics such as bevacizumab, which are widely used in cancer treatment, commonly leads to hypertension. Moreover, bevacizumab-induced hypertension is associated with improved clinical outcomes in several cancers. We retrospectively analyzed 89 patients with histologically confirmed advanced gastric cancer who received the human monoclonal anti-VEGF receptor-2 antibody ramucirumab plus paclitaxel at our hospital between June 2015 and October 2016 to evaluate the impact of treatment-associated hypertension occurring within the first two treatment cycles (“early hypertension”) on outcome. The objective response rate was 40%, median progression-free survival was 5.4 months, and overall survival was 10.4 months, which is similar to previous reports. Early hypertension in patients who received more than two cycles of ramucirumab + paclitaxel was associated with longer progression-free and overall survival. Objective response rates were also higher in patients with early hypertension. These data indicate that early hypertension may be predictive of better outcomes in gastric cancer patients who receive ramucirumab + paclitaxel treatment.

Krebs-2 solid carcinoma was cured using a new “3+1” strategy for eradication of Krebs-2 tumor-initiating stem cells. This strategy was based on synchronization of these cells in a treatment-sensitive phase of the cell cycle. The synchronization mechanism, subsequent destruction of Krebs-2 tumor-initiating stem cells, and cure of mice from a solid graft were found to depend on the temporal profile of the interstrand cross-link repair cycle. Also, the temporal profile of the Krebs-2 interstrand repair cycle was found to have a pronounced seasonal cyclicity at the place of experiments (Novosibirsk, Russia). As a result, the therapeutic effect that is based on application of the described strategy, originally developed for the “winter repair cycle” (November−April), is completely eliminated in the summer period (June−September). We conclude that оne of the possible and the likeliest reasons for our failure to observe the therapeutic effects was the seasonal cyclicity in the duration of the interstrand repair cycle, the parameter that is central to our strategy.

// Philip Carter 1 , Costi Alifrangis 2 , Biancastella Cereser 1 , Pramodh Chandrasinghe 1, 3 , Lisa Del Bel Belluz 1 , Nina Moderau 1 , Fotini Poyia 1 , Lee S. Schwartzberg 4 , Neha Tabassum 1 , Jinrui Wen 1 , Jonathan Krell 1 and Justin Stebbing 1 1 Department of Surgery and Cancer, Imperial College, London, UK 2 Department of Oncology, University College Hospital, London, UK 3 Department of Surgery, University of Kelaniya, Kelaniya, Sri Lanka 4 West Cancer Center, The University of Tennessee, Memphis, USA Correspondence to: Philip Carter, email: phil.carter@imperial.ac.uk Keywords: tumor profiling; breast cancer; cancer treatment Received: July 29, 2017 Accepted: October 28, 2017 Epub: February 24, 2018 Published: April 03, 2018 ABSTRACT We used data obtained by Caris Life Sciences, to evaluate the benefits of tailoring treatments for a breast carcinoma cohort by using tumor molecular profiles to inform decisions. Data for 92 breast cancer patients from the commercial Caris Molecular Intelligence database was retrospectively divided into two groups, so that the first always followed treatment recommendations, whereas in the second group all patients received at least one drug after profiling that was predicted to lack benefit. The biomarker and drug associations were based on tests including fluorescent in situ hybridization and DNA sequencing, although immunohistochemistry was the main test used. Patients whose drugs matched those recommended according to their tumor profile had an average overall survival of 667 days, compared to 510 days for patients that did not (P=0.0316). In the matched treatment group, 26% of patients were deceased by the last time of monitoring, whereas this was 41% in the unmatched group (P=0.1257). We therefore confirm the ability of tumor molecular profiling to improve survival of breast cancer patients. Immunohistochemistry biomarkers for the androgen, estrogen and progesterone receptors were found to be prognostic for survival.

An extremely high cancer incidence and the hypersensitivity to DNA crosslinking agents associated with Fanconi Anemia (FA) have marked it to be a unique genetic model system to study human cancer etiology and treatment, which has emerged an intense area of investigation in cancer research. However, there is limited information about the relationship between the mutated FA pathway and the cancer development or/and treatment in patients without FA. Here we analyzed the mutation rates of the seventeen FA genes in 68 DNA sequence datasets. We found that the FA pathway is frequently mutated across a variety of human cancers, with a rate mostly in the range of 15 to 35 % in human lung, brain, bladder, ovarian, breast cancers, or others. Furthermore, we found a statistically significant correlation (p < 0.05) between the mutated FA pathway and the development of human bladder cancer that we only further analyzed. Together, our study demonstrates a previously unknown fact that the mutated FA pathway frequently occurs during the development of non-FA human cancers, holding profound implications directly in advancing our understanding of human tumorigenesis as well as tumor sensitivity/resistance to crosslinking drug-relevant chemotherapy.

Pardaxin is an antimicrobial peptide of 33 amino acids, originally isolated from marine fish. We previously demonstrated that pardaxin has anti-tumor activity against murine fibrosarcoma, both in vitro and in vivo. In this study, we examined the anti-tumor activity, toxicity profile, and maximally-tolerated dose of pardaxin treatment in dogs with different types of refractory tumor. Local injection of pardaxin resulted in a significant reduction of perianal gland adenoma growth between 28 and 38 days post-treatment. Surgical resection of canine histiocytomas revealed large areas of ulceration, suggesting that pardaxin acts like a lytic peptide. Pardaxin treatment was not associated with significant variations in blood biochemical parameters or secretion of immune-related proteins. Our findings indicate that pardaxin has strong therapeutic potential for treating perianal gland adenomas in dogs. These data justify the veterinary application of pardaxin, and also provide invaluable information for veterinary medicine and future human clinical trials.

Neuro-oncology is a growing new subspeciality with a strong interdisciplinary character. This position paper explains the role of neurology in the multidisciplinary field of neurosurgeons, radiotherapists and general oncologists, dealing with neuro-oncological patients. The paper delineates the varied spectrum of the field of neuro-oncology which expands from primary brain tumours, to metastatic and non-metastatic effects of systemic cancer on the central and peripheral nervous system, neurotoxicity due to cancer treatment and issues of quality of life. It has been written by the scientific neuro-oncology panel of the European Federation of Neurological Societies (EFNS) to delineate the situation of neuro-oncology in Europe, and facilitate the understanding and implementation of this subspeciality in the future.

Phototherapy has emerged as a novel therapeutic modality for cancer treatment, but its low therapeutic efficacy severely hinders further extensive clinical translation and application. This study reports amplifying the phototherapeutic efficacy by constructing a near‐infrared (NIR)‐responsive multifunctional nanoplatform for synergistic cancer phototherapy by a single NIR irradiation, which can concurrently achieve mitochondria‐targeting phototherapy, synergistic photothermal therapy (PTT)/photodynamic therapy (PDT), self‐sufficient oxygen‐augmented PDT, and multiple‐imaging guidance/monitoring. Perfluorooctyl bromide based nanoliposomes are constructed for oxygen delivery into tumors, performing the functions of red blood cells (RBCs) for oxygen delivery (“Nano‐RBC” nanosystem), which can alleviate the tumor hypoxia and enhance the PDT efficacy. The mitochondria‐targeting performance for enhanced and synergistic PDT/PTT is demonstrated as assisted by nanoliposomes. In particular, these “Nano‐RBCs” can also act as the contrast agents for concurrent computed tomography, photoacoustic, and fluorescence multiple imaging, providing the potential imaging capability for phototherapeutic guidance and monitoring. This provides a novel strategy to achieve high therapeutic efficacy of phototherapy by the rational design of multifunctional nanoplatforms with the unique performances of mitochondria targeting, synergistic PDT/PTT by a single NIR irradiation (808 nm), self‐sufficient oxygen‐augmented PDT, and multiple‐imaging guidance/monitoring.

There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regulation on tumor microenvironment through activation of tumor infiltrating T lymphocytes and natural killer cells, promotion of cytokines secretion of IFN-γ and IL-12, and down-regulation of immunosuppressive myeloid-derived suppressor cells, cytokine IL-10 and TGF-β. ATRA/DOX/IL-2 co-loaded dHMLB demonstrated significant tumor growth and metastasis inhibition, and also exhibited favorable biodegradability and safety. This nanoplatform has great potential in developing a feasible strategy to remodel tumor immune microenvironment and achieve enhanced antitumor effect.

Near infrared photoimmunotherapy (NIR-PIT) is a newly-developed cancer therapy in which a monoclonal antibody is conjugated to a near-infrared photoabsorber, IR700 to form an antibody photoabsorber conjugate (APC). After the APC binds to cancer cells expressing the cognate antigen, exposure to NIR light results in rapid, highly selective necrotic cell death of the cancer cells with minimal off-target effects. Several hours after NIR-PIT, the tumor vessels become supraphysiologically permeable and circulating APC can therefore readily leak into the already-treated tumor space where it can bind with viable cancer cells that is called super-enhanced permeability and retention effect. The presence of the SUPR effect after NIR-PIT has prompted regimens in which there is a repeat exposure of NIR light 24 hours after the initial NIR-PIT to take advantage of the leakage of additional APC deeper into the tumor. However, this post-treatment APC penetration was fully induced within 3 hours, therefore, it is possible that repeated exposures of NIR light could be administered much earlier than 24 hours and still produce the same effects. To test this idea, we compared several modes of delivering additional doses of light after initial NIR-PIT. We found that repeated exposures of NIR light starting 3 hours after initial NIR-PIT produced equal or superior results to more delayed exposures of NIR light. This finding has practical implications of an easy-to-perform regimen as repeated light exposures could be performed during a single day rather than extending the procedure over two days which is the current recommendation.

Introduction : Secondary lymphedema affects approximately 40% of women treated for breast cancer and is recognized as a major problem associated with the therapy of malignant tumors. Consequently, new therapeutic methods are constantly being sought to effectively eliminate the condition. One of the new forms of edema management, especially in the initial stages of edematous development, is Kinesiology Taping (KT). Aim of the study : The aim of the study was to assess the effects of KT applications on the extent of lymphedema of the upper extremity in women post cancer treatment. Material and methods: The study group consisted of 28 women after axillary lymphadenectomy due to breast cancer. All the patients were diagnosed with grade I secondary lymphedema. Kinesiology Taping was applied to a total of 14 randomly selected women. The remaining 14 patients constituted a control group. The extent of lymphedema was measured using a centimeter tape and Limb Volumes Professional 5.0 software. Results : A significant reduction in the extent of lymphedema (p = 0.0009) was achieved in the KT group between baseline and post-treatment assessments. No such reduction, however, was found in the control group (p = 0.36). Conclusions : Kinesiology Taping applications are an effective method of early-stage edema management. Kinesiology Taping may be a safe new therapeutic option in patients who are contraindicated for the use of other methods.

Background: Finding the correct medical information in a flood of information from the internet is a significant issue for patients with cancer. Objective: We investigated the reliability of the information on cancer treatment methods available on the internet based on an evaluation by medical oncologists, medical students, and cancer survivors. Methods: Using Google and Yahoo as the search engines, we carried out the information search using 2 keywords, “cancer treatment” and “cancer cure,” and the top 20 information sites were identified. A similar search was conducted on 5 types of cancer. The reliability of the information presented was rated on a 3-level scale (A, B, or C). Level A referred to reliable sites (providing information complying with the clinical practice guidelines for various types of cancer), Level B included sites not falling under either Level A or Level C, and Level C comprised dangerous or harmful sites (providing information on treatment not approved by the regulatory authority in Japan and bombastic advertisements without any relevant clinical evidence). The evaluation was conducted by medical oncologists, medical students, and cancer survivors. The consistency of the information reliability level rating between the medical students or cancer survivors with that of the medical oncologists was assessed by using the kappa value. Results: A total of 247 sites were evaluated for reliability. The ratings provided by the medical students’ group were as follows: Level A, 12.1% (30/247); Level B, 56.3% (139/247); and Level C, 31.6% (78/247). The ratings provided by the cancer survivors’ group were as follows: Level A, 16.8% (41/244); Level B, 44.7% (109/244); and Level C, 38.5% (94/244). The ratings provided by the oncologists’ group were as follows: Level A, 10.1% (25/247); Level B, 51.4% (127/247); and Level C, 38.5% (95/247). The intergroup rating consistency between the medical students’ group and oncologists’ group was 87.4% (216/247, kappa=0.77) and that between the cancer survivors’ group and oncologists’ group was 76.2% (186/244, kappa=0.61). Conclusions: Of the investigated sites providing information on cancer treatment on the internet, the percentage of sites that seemed to provide harmful information was much higher than that of sites providing reliable information. The reliability level rating was highly consistent between the medical students’ group and the medical oncologists’ group and also between the cancer survivors’ group and the medical oncologists’ group.

BackgroundOver the last two decades, the incidence and mortality rates of gynecologic cancers have increased at a constant rate in China. Gynecologic cancers have become one of the most serious threats to women’s health in China. With the widespread use of social media, an increasing number of individuals have employed social media to produce, seek, and share cancer-related information. However, health information on social media is not always accurate. Health, and especially cancer-related, misinformation has been widely spread on social media, which can affect individuals’ attitudinal and behavioral responses to cancer.ObjectiveThe aim of this study was to examine the nature and diffusion of gynecologic cancer–related misinformation on Weibo, the Chinese equivalent of Twitter.MethodsA total of 2691 tweets related to 2 gynecologic cancers—breast cancer and cervical cancer—posted on Weibo from June 2015 to June 2016 were extracted using the Python Web Crawler. Two medical school graduate students with expertise in gynecologic diseases were recruited to code the tweets to differentiate between true information and misinformation as well as to identify the types of falsehoods. The diffusion characteristics of gynecologic cancer–related misinformation were compared with those of the true information.ResultsWhile most of the gynecologic cancer–related tweets provided medically accurate information, approximately 30% of them were found to contain misinformation. Furthermore, it was found that tweets about cancer treatment contained a higher percentage of misinformation than prevention-related tweets. Nevertheless, the prevention-related misinformation diffused significantly more broadly and deeply than true information on social media.ConclusionsThe findings of this study suggest the need for controlling and reducing the cancer-related misinformation on social media with the efforts from both service providers and medical professionals. More specifically, it is important to correct falsehoods related to the prevention of gynecologic cancers on social media and increase individuals’ capacity to assess the veracity of Web-based information to curb the spread and thus minimize the consequences of cancer-related misinformation.

Photothermal therapy (PTT) for cancer treatment is the use of heat between 41 and 45 °C to damage cancer cells. As a new type of transducer agent for PTT of cancer, CuS nanoparticles have several advantages. The most favorable features are the low cost, simple, and easy preparation and small size for targeting. However, the CuS nanoparticle PTT efficacy needs to be improved for practical applications. In this study, the CuS nano-PTT efficiency is enhanced via the local field enhancement from Ag nanoparticle surface plasmon coupling. The results show that absorbance of CuS nanoparticles in Ag/CuS nanocomposites is enhanced about four times by Ag nanoparticle surface plasmon coupling. Consequently, the PTT efficacy is enhanced and a power of 0.6 W/cm2 with a 980-nm laser is sufficient for Ag/CuS nano-PTT activation for cancer treatment in vitro observations.

There are an increasing number of studies devoted to the identification of associations between anticancer drug efficacy and toxicity and common polymorphisms present in the patients’ genome. However, many articles presenting the results of such studies do not bring the simple and necessary background information allowing the evaluation of the relevance of the study, its significance and its potential importance for patients’ treatment. This position paper first addresses clinical oncologists with the aim of giving them the basic knowledge on pharmacogenetics and on the potential use of gene polymorphisms as predictive biomarkers in routine and clinical research. A secondary objective is to give molecular biologists some recommendations on how to conceive protocols and how to publish their results when they develop pharmacogenetic studies appended to clinical trials or with autonomous goals.

Despite the development of new antineoplastic agents for the treatment of colorectal cancer (CRC), oxaliplatin and fluoropyrimidines remain the most commonly employed drugs for the treatment of both early and advanced disease. Intrinsic or acquired resistance is, however, an important limitation to pharmacological therapy, and the development of chemosensitization strategies constitute a major goal with important clinical implications. In the present work, we determined that high levels of activated Src kinase, measured as phospho-Src at the Tyr419 residue in CRC cell lines, can promote colorectal carcinoma cell resistance to oxaliplatin, but not to 5-fluorouracil (5FU), and that inhibition of this protein restores sensitivity to oxaliplatin. Similar results were observed with in vivo patient-derived xenograft (PDX) models that were orthotopically grown in murine livers. In PDX tumor lines derived from human CRC liver metastasis, dasatinib, a Src inhibitor, increases sensitivity to oxaliplatin only in tumors with high p-Src. However, dasatinib did not modify sensitivity to 5FU in any of the models. Our data suggest that chemoresistance induced by p-Src is specific to oxaliplatin, and that p-Src levels can be used to identify patients who may benefit from this combination therapy. These results are relevant for clinicians as they identify a novel biomarker of drug resistance that is suitable to pharmacological manipulation., The authors thank the donors and HUVR-IBiS Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT13/0010/0056) for the human specimens used in this study. We also thank Jorge Martin-Perez for the generous gift of Src gene. The AC lab was supported by grants from the Spanish Ministry of Economy and Competitivity, Plan Nacional de I+D+I 2008-2011, Plan Estatal de I+D+I 2013-2016, ISCIII (Fis: PI12/00137, PI13/02295, PI15/00045, RTICC: RD12/0036/0028) co-funded by FEDER from Regional Development European Funds (European Union), Consejeria de Ciencia e Innovacion (CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI-0306-2012 and PI-0096-2014).

// Wei Chen 1, 4 , Hui Ding 2 , Pengmian Feng 3 , Hao Lin 2, 4 , Kuo-Chen Chou 4, 5 1 Department of Physics, School of Sciences, Center for Genomics and Computational Biology, North China University of Science and Technology, Tangshan, China 2 Key Laboratory for Neuro-Information of Ministry of Education, Center of Bioinformatics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China 3 School of Public Health, North China University of Science and Technology, Tangshan, China 4 Gordon Life Science Institute, Belmont, Massachusetts, United States of America 5 Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia Correspondence to: Wei Chen, e-mail: wchen@gordonlifescience.org , chenweiimu@gmail.com Hao Lin, e-mail: hlin@uestc.edu.cn Kuo-Chen Chou, e-mail: kcchou@gordonlifescience.org Keywords: anticancer peptides, PseAAC, g-gap dipeptide mode, incremental feature selection, iACP webserver Received: January 06, 2016 Accepted: February 11, 2016 Published: March 01, 2016 ABSTRACT Cancer remains a major killer worldwide. Traditional methods of cancer treatment are expensive and have some deleterious side effects on normal cells. Fortunately, the discovery of anticancer peptides (ACPs) has paved a new way for cancer treatment. With the explosive growth of peptide sequences generated in the post genomic age, it is highly desired to develop computational methods for rapidly and effectively identifying ACPs, so as to speed up their application in treating cancer. Here we report a sequence-based predictor called iACP developed by the approach of optimizing the g-gap dipeptide components. It was demonstrated by rigorous cross-validations that the new predictor remarkably outperformed the existing predictors for the same purpose in both overall accuracy and stability. For the convenience of most experimental scientists, a publicly accessible web-server for iACP has been established at http://lin.uestc.edu.cn/server/iACP , by which users can easily obtain their desired results.

Early detection and subsequent complete surgical resection are among the most efficient methods for treating cancer. However, low detection sensitivity and incomplete tumor resection are two challenging issues. Nanoparticle-based imaging-guided surgery has proven promising for cancer-targeted imaging and subsequent debulking surgery. Particularly, the use of near infrared (NIR) fluorescent probes such as NIR quantum dots (QDs) allows deep penetration and high sensitivity for tumor detection. In this study, NIR-emitting CdTe QDs (maximum fluorescence emission peak at 728 nm) were synthesized with a high quantum yield (QY) of 38%. The tumor-specific QD bioconjugates were obtained by attaching cyclic Arg-Gly-Asp peptide (cRGD) to the surface of synthesized QDs, and then injected into U87 MG tumor-bearing mice via tail veins for tumor-targeted imaging. The tumor and its margins were visualized and distinguished by NIR QD bioconjugates, and tumor resection was successfully accomplished via NIR guidance using a Fluobeam-700 NIR imaging system. Our work indicates that the synthesized tumor-specific NIR QDs hold great promise as a potential fluorescent indicator for intraoperative tumor imaging.

PURPOSE: Pre-menopausal women with cancer are at risk of therapy-associated infertility, premature menopause, and sexual dysfunction. However, it is unknown whether oncologists adequately address these risks during treatment planning. We conducted a study to evaluate physician-patient discussions addressing the impact of cancer treatment and actual treatment effects on fertility, menopause status, and general sexual health. METHODS: A questionnaire was administered in four oncology clinics specializing in breast, gynecologic, general hematology-oncology, and blood and marrow transplantation (BMT) cancer care at a single institution. Eligible participants were pre-menopausal at the time of diagnosis and either actively receiving or within 24 months from completion of treatment. Participants completed the questionnaire at enrollment and at 1-year follow-up. RESULTS: Of the 104 eligible women, a majority were satisfied with the quality (68%) and length (66%) of reproductive health discussions, with the highest satisfaction levels in the gynecologic cancer clinic (85%) and the lowest levels in the BMT clinic (53%). Fertility preservation was desired by 20% of women, including some >40 years old. Women were more interested in discussing treatment impact on menopause status and sexual health than fertility. Rates of discussions on treatment impact on sexual health were low despite 77% of women reporting severe sexual dysfunction at 1-year follow-up. CONCLUSIONS: One-third of women are dissatisfied with the quality and length of discussions regarding the impact of cancer treatment on reproductive health. There is notably inadequate counseling on the effect of treatment on fertility in women > 40 and on sexual function in all women. Oncologists must offer better resources and improve communication on the effect of treatment on reproductive health to pre-menopausal women with cancer.

The application of nanomaterial in cancer treatment is promising and intriguing. Anti-tumor immunotherapy has the potential to significantly improve the prognosis of cancer treatment, though the efficacy of immunotherapy generally needs further improvement. One way to improve the efficacy is using immune adjuvants, but the adjuvants for anticancer immunotherapy have to be more potent than for prophylactic vaccines. Here, we report that compared to conventional alum adjuvant, aluminum oxide nanoparticles (nano-alum) may further enhance the anticancer effects of an immunotherapy that employs tumor cell vaccine (TCV). The average tumor size tends to be lower in animals that receive the combinational treatment of nano-alum and TCV. The anticancer cytotoxicity by the lymphocytes was also significantly higher in the treatment group that received both TCV and nano-alum. These results suggest that nano-alum may potentially serve as a potent immune adjuvant and have prospective applications in anticancer immunotherapy.

// Barbara Christy 1,5,6,* , Marco Demaria 7,* , Judith Campisi 7 , Jing Huang 8 , Diane Jones 1 , Sherry G. Dodds 1 , Charnae Williams 1 , Gene Hubbard 2 , Carolina B. Livi 1,9 , Xiaoli Gao 3 , Susan Weintraub 3 , Tyler Curiel 4,5 , Z. Dave Sharp 1,5,6 and Paul Hasty 1,5,6 1 Departments of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA 2 Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA 3 Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA 4 Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA 5 Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA 6 Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA 7 Buck Institute for Research on Aging, Novato, CA, USA 8 Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA 9 Current address: Agilent Technologies, Inc., Santa Clara, CA, USA * These authors have contributed equally to this work Correspondence to: Paul Hasty, email: // Keywords : mTOR, p53, rapamycin, longevity, SASP Received : May 18, 2015 Accepted : June 14, 2015 Published : June 23, 2015 Abstract Mechanistic target of rapamycin (mTOR) is a kinase found in a complex (mTORC1) that enables macromolecular synthesis and cell growth and is implicated in cancer etiology. The rapamycin-FK506 binding protein 12 (FKBP12) complex allosterically inhibits mTORC1. In response to stress, p53 inhibits mTORC1 through a separate pathway involving cell signaling and amino acid sensing. Thus, these different mechanisms could be additive. Here we show that p53 improved the ability of rapamycin to: 1) extend mouse life span, 2) suppress ionizing radiation (IR)-induced senescence-associated secretory phenotype (SASP) and 3) increase the levels of amino acids and citric acid in mouse embryonic stem (ES) cells. This additive effect could have implications for cancer treatment since rapamycin and p53 are anti-oncogenic.