13 October 2017 (Friday) - ASH Update

The American Society of Hematology sent me a few snippets today:


FEATURES
Mining the “Gold Rush” of Immunotherapy Clinical Trials
As the number of immunotherapy clinical trials grows, so do the obstacles and challenges – including the need to ensure meaningful results.

Entering A New Era of Immunotherapy
The first approval of a chimeric antigen receptor T-cell therapy marks a shift in the future of the immunotherapy field.
NEWLY APPROVED DRUGS
The Year in Drug Approvals
The excitement over immunotherapy for cancer treatment shows no signs of waning, with several agents approved by the U.S. Food and Drug Administration this year.
IN THE PIPELINE
The Immunotherapy Pipeline
Dozens of immunotherapeutic agents are under investigation for the treatment of malignant and non-malignant hematologic conditions.

All good stuff...

13 October 2017 (Friday) - World Thrombosis Day


It is World Thrombosis Day today. Rather than posting all sorts of learned journal references I shall instead post something that a friend posted to Facebook this morning:

World Thrombosis day today... Shortly I’ve got Nurses coming out to try and take my blood and see if My DDimer has gone back down after it was raised again on Saturday. It’s almost been 2 months since I was rushed to A&E with Blood Clots on my Lungs and me and my hubby sat in tears last night thinking how much our life has changed! I hope one day for everyone’s sake I can get some normality back in my life.


This rather put it all into perspective for me today…

13 October 2017 (Friday) - IBMS Vision

The IBMS sent me an email today outlining their strategy for the next few years. You can read it by clicking here.

I have read it. Several times. There are six pages of words… In all honesty it means nothing to me. Once I was an IBMS rep; we all knew what the IBMS was, and what it did. It didn’t have (or need) mission statements.
It is nonsense like  this which puts me off of getting involved too much with the IBMS.
Is that wrong of me?


13 October 2017 (Friday) - A Poll


Here’s a rather silly poll I received from the Lablogatory people today. “How many cases of thalassemia does your laboratory see per year?


I suspect they mean “thalassaemia major”; beta thalassaemia minor isn’t uncommon, and come to that neither is alpha thalassaemia minor. I peobably see a case of each at least once a week…

12 October 2017 (Thursday) - Transfusion Evidence Library email

The Transfusion Evidence Library people sent me their monthly update today… loads of articles. Some of interest, others not (quite) so…

Click on any of the links below to view the article in the Transfusion Evidence Library database. Enjoy your update!

Clinical Commentaries

11 October 2017 (Wednesday) - Oncologist Newsletter

The Oncologist Newsletter appeared in my in-box this morning:



Precision Medicine Clinic: Molecular Tumor Board

Exceptional Response with Immunotherapy in a Patient with Anaplastic Thyroid Cancer

Revathi Kollipara, Bryan Schneider, Milan Radovich, Sunil Babu, Patrick J. Kiel
This article describes the case of a 52-year-old male who was diagnosed with anaplastic thyroid cancer. The patient harbored a V600E mutation in BRAF and a PD-L1 positivity in both the tumor and the tumor infiltrating lymphocytes. Diagnosis and treatment details are reported.

Clinical Trial Results

A Phase II Study with Lead-In Safety Cohort of 5-Fluorouracil, Oxaliplatin, and Lapatinib in Combination with Radiation Therapy as Neoadjuvant Treatment for Patients with Localized HER2-Positive Esophagogastric Adenocarcinomas

Gregg Shepard, Edward R. Arrowsmith, Patrick Murphy, John H. Barton, Jr., James D. Peyton, Mark Mainwaring, Laura Blakely, Noel A. Maun, Johanna C. Bendell

Pregabalin for the Prevention of Oxaliplatin-Induced Painful Neuropathy: A Randomized, Double-Blind Trial

Daniel Ciampi de Andrade, Manoel Jacobsen Teixeira, Ricardo Galhardoni, Karine S.L. Ferreira, Paula Braz Mileno, Nathalia Scisci, Alexandra Zandonai, William G.J. Teixeira, Daniel F. Saragiotto, Valquíria Silva, Irina Raicher, Rubens Gisbert Cury, Ricardo Macarenco, Carlos Otto Heise, Mario Wilson Iervolino Brotto, Alberto Andrade de Mello, Marcelo Zini Megale, Luiz Henrique Curti Dourado, Luciana Mendes Bahia, Antonia Lilian Rodrigues, Daniella Parravano, Julia Tizue Fukushima, Jean-Pascal Lefaucheur, Didier Bouhassira, Evandro Sobroza, Rachel P. Riechelmann, Paulo M. Hoff, and PreOx Workgroup (Fernanda Valério da Silva, Thais Chile, Camila S. Dale, Daniela Nebuloni, Luiz Senna, Helena Brentani, Rosana L. Pagano, Ângela M. de Souza)

A Phase II Trial Evaluating the Safety of Rapid Infusion of Ofatumumab in Patients with Previously Treated Chronic Lymphocytic Leukemia

William Donnellan, Jesus G. Berdeja, Diana Shipley, Edward R. Arrowsmith, David Wright, Scott Lunin, Richard Brown, James H. Essell, Ian W. Flinn

Phase II Trial of Sorafenib in Combination with Capecitabine in Patients with Hepatocellular Carcinoma: INST 08-20

Yehuda Patt, Cristhiam Rojas-Hernandez, Houman Mohammad Fekrazad, Pranshu Bansal, Fa Chyi Lee

Breast Cancer

Efficacy and Safety of Pertuzumab and Trastuzumab Administered in a Single Infusion Bag, Followed by Vinorelbine: VELVET Cohort 2 Final Results

Michael Andersson, José M. López-Vega, Thierry Petit, Claudio Zamagni, Valerie Easton, Julia Kamber, Eleonora Restuccia, Edith A. Perez
The final efficacy and safety results are reported for the VELVET Cohort 2 trial, which investigated the coinfusion of pertuzumab and trastuzumab in a single infusion bag, followed by vinorelbine.

Randomized Controlled Trial of a Home-Based Walking Program to Reduce Moderate to Severe Aromatase Inhibitor-Associated Arthralgia in Breast Cancer Survivors

Kirsten A. Nyrop, Leigh F. Callahan, Rebecca J. Cleveland, Liubov L. Arbeeva, Betsy S. Hackney, Hyman B. Muss
For most breast cancer survivors experiencing aromatase inhibitor-associated arthralgia (AIAA), pharmacological remedies such as analgesics and antidepressants provide little or no joint symptom relief, and these medications have their own adverse side effects. There is a need to identify effective, easy-to-use, sustainable, and safe alternative or adjunctive approaches to AIAA management. This article describes an evidence-based walking program that is effective in reducing symptoms in adults with arthritis and investigates whether the program could have similar benefits for women experiencing AIAA.

Cancer Diagnostics and Molecular Pathology

Clinical Application of Targeted Deep Sequencing in Solid-Cancer Patients; Utility of Targeted Deep Sequencing for Biomarker-Selected Clinical Trial

Seung Tae Kim, Kyoung-Mee Kim, Nayoung K.D. Kim, Joon Oh Park, Soomin Ahn, Jae-Won Yun, Kyu-Tae Kim, Se Hoon Park, Peter J. Park, Hee Cheol Kim, Tae Sung Sohn, Dong Il Choi, Jong Ho Cho, Jin Seok Heo, Wooil Kwon, Hyuk Lee, Byung-Hoon Min, Sung No Hong, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Woong-Yang Park, Jeeyun Lee
Advances in sequencing technologies and improved algorithms for detecting specific molecular aberrations make it possible to perform biomarker-driven clinical trials. The analytical sensitivity and clinical validity have not yet been demonstrated in a large cohort. This article describes the implementation of a targeted-sequencing panel in a precision oncology clinic and the feasibility of a clinic-based molecular screening program.

Gastrointestinal Cancer

TERT Promoter Hypermethylation in Gastrointestinal Cancer: A Potential Stool Biomarker

Li Liu, Cheng Liu, Omid Fotouhi, Yidong Fan, Kun Wang, Chuanyou Xia, Benkang Shi, Guangyong Zhang, Kexin Wang, Feng Kong, Catharina Larsson, Sanyuan Hu, Dawei Xu
This study aimed to determine whether the TERT promoter methylation differs between gastrointestinal cancer and normal gastrointestinal tissues and, if so, whether the TERT promoter methylation analysis in stool is useful for screening of gastrointestinal cancer.

Geriatric Oncology

Association of Pre-Chemotherapy Peripheral Blood Pro-Inflammatory and Coagulation Factors with Physical Function in Women with Breast Cancer

Yuan Yuan, Nilesh Vora, Can-Lan Sun, Daneng Li, David Smith, Joanne Mortimer, The-Hang Luu, George Somlo, James Waisman, Joseph Chao, Vani Katheria, Timothy Synold, Vivi Tran, Shu Mi, Tao Feng, Abrahm Levi, Anait Arsenyan, Jennifer Choi, Laura Zavala, Susan Yost, Arti Hurria
Breast cancer is a disease associated with aging. Before initiation of chemotherapy, an assessment of functional reserve is needed; however, simple performance assessment scores may not reflect the diverse nature of physical function and risk of toxicity among older adults. The focus of this article is on understanding the association between pre-chemotherapy biomarkers (IL-6, CRP, and D-dimer) and measures of physical function.

Global Health and Cancer

Implementation of a School-Based Educational Program to Increase Breast Cancer Awareness and Promote Intergenerational Transmission of Knowledge in a Rural Mexican Community

Enrique Soto-Perez-de-Celis, David D. Smith, Maria Patricia Rojo-Castillo, Arti Hurria, Alba Milena Pavas-Vivas, Rina Gitler-Weingarten, Alejandro Mohar, Yanin Chavarri-Guerra
Breast cancer mortality rates in low- and middle-income countries are higher than in the developed world. Programs aimed at enhancing education and awareness of breast cancer are a critical strategy to overcoming barriers to timely diagnosis in these countries. This article reports a program designed to educate adolescents on breast cancer with the end goal of promoting intergenerational transmission of breast cancer-related knowledge to their older female relatives.

Medical Ethics

Patient-Driven Second Opinions in Oncology: A Systematic Review

Marij A. Hillen, Niki M. Medendorp, Joost G. Daams, Ellen M.A. Smets
An increasing number of cancer patients appears to seek a second opinion about diagnosis or treatment. This systematic review examines the available empirical evidence on patient-initiated second opinions in oncology and provides recommendations to clinicians for optimal communication about second opinions.

New Drug Development and Clinical Pharmacology

Fixed Dosing of Monoclonal Antibodies in Oncology

Jeroen J.M.A. Hendrikx, John B.A.G. Haanen, Emile E. Voest, Jan H.M. Schellens, Alwin D.R. Huitema, Jos H. Beijnen
In the field of oncology, most drugs are administered in a body–size-based dosing schedule instead of a fixed dose for all patients. This article presents the advantages of fixed dosing of monoclonal antibodies, arguing in favor of fixed dosing schemes for all currently approved antibodies in oncology.

Radiation Oncology

Pulmonary Function Changes After Radiotherapy for Lung or Esophageal Cancer: A Systematic Review Focusing on Dose-Volume Parameters

Anne G.H. Niezink, Renske A. de Jong, Christina T. Muijs, Johannes A. Langendijk, Joachim Widder
Radiation-induced lung toxicity remains a challenge in thoracic radiotherapy. This systematic review focuses on radiation dose-volume histogram parameters for lung and heart as predictors for changes in FEV1 and diffusion capacity after radiotherapy for lung or esophageal cancer.

Sarcomas

Localized Adult Ewing Sarcoma: Favorable Outcomes with Alternating Vincristine, Doxorubicin, Cyclophosphamide, and Ifosfamide, Etoposide (VDC/IE)-Based Multimodality Therapy

Jennifer L. Pretz, Constance M. Barysauskas, Suzanne George, Jason L. Hornick, Chandrajit. P. Raut, Yen-Lin E. Chen, Karen J. Marcus, Edwin Choy, Francis Hornicek, John E. Ready, Thomas F. DeLaney, Elizabeth H. Baldini
Although typically considered a pediatric disease, Ewing sarcoma can occur adults. Current standard treatment for localized Ewing sarcoma is a multimodality approach, combining chemotherapy and local therapy consisting of surgery and/or radiation therapy. This article evaluates outcomes for adults with localized Ewing sarcoma treated exclusively with cyclophosphamide, doxorubicin, and vincristine followed by ifosfamide and etoposide in combination with local therapy.

Vincristine, Ifosfamide, and Doxorubicin for Initial Treatment of Ewing Sarcoma in Adults

Michael J. Wagner, Vancheswaran Gopalakrishnan, Vinod Ravi, J. Andrew Livingston, Anthony P. Conley, Dejka Araujo, Neeta Somaiah, Maria A. Zarzour, Ravin Ratan, Wei-Lien Wang, Shreyaskumar R. Patel, Alexander Lazar, Joseph A. Ludwig, Robert S. Benjamin
Ewing sarcoma is rare in adults, and there are no dedicated clinical trials in the adult population. This article reviews the results of therapy with vincristine, ifosfamide, and doxorubicin in the multidisciplinary treatment of adults with Ewing sarcoma.

Symptom Management and Supportive Care

A Predictive Score for Thrombosis Associated with Breast, Colorectal, Lung, or Ovarian Cancer: The Prospective COMPASS–Cancer-Associated Thrombosis Study

Grigoris T. Gerotziafas, Ali Taher, Hikmat Abdel-Razeq, Essam AboElnazar, Alex C. Spyropoulos, Salem El Shemmari, Annette K. Larsen, Ismail Elalamy, on behalf of the COMPASS–CAT Working Group
The COMPASS-CAT study was undertaken in outpatients with breast, colon, lung, or ovarian cancer. The aim of the study was to identify the most relevat risk factors for symptomatic thromboembolism and to develop a risk assessment model applicable to patients after the initiation of anticancer treatment.

Immune-Related Adverse Events as a Biomarker in Non-Melanoma Patients Treated with Programmed Cell Death 1 Inhibitors

Julia Judd, Matthew Zibelman, Elizabeth Handorf, John O'Neill, Chethan Ramamurthy, Sasini Bentota, Jamie Doyle, Robert G. Uzzo, Jessica Bauman, Hossein Borghaei, Elizabeth R. Plimack, Ranee Mehra, Daniel M. Geynisman
Immune checkpoint inhibitors are a novel class of immunotherapeutic agents being used in clinical practice for many advanced malignancies. Checkpoint blockade targeting the programmed cell death 1 receptor or its primary ligand with pembrolizumab, nivolumab, or atezolizumab has received U.S. Food and Drug Administration approval for the treatment ofmetastatic melanoma, non-small cell lung cancer, renal cell carcinoma, Hodgkin's lymphoma, head and neck squamous cell carcinoma, and urothelial carcinoma. Considering that checkpoint blockade treatments now extend to tumor types beyond melanoma, a study was conducted to evaluate whether the development of immune-related adverse events correlates with treatment response in other cancer subtypes.

Narratives in Oncology

Ten Months: One Patient's Story of Stage IV Cancer

Nora K. Murphy
Originally presented as part of the 20th Anniversary of Palliative Care at Massachusetts General Hospital, this narrative is one patient's story of stage IV cancer.

11 October 2017 (Wednesday) - Malaria

The nice people at Wiley sent me a link to a malaria journal today. Bearing in mind I’m typing this up having just confirmed a case of malaria I found this particularly relevant.

Commentaries

Article Category
COMMENTARIES

Malaria, metabolism and mathematical models

Authors
Rita Gemayel
First Published:
Vol:
284,
Pages:
2553–2555
DOI:
10.1111/febs.14161
image
Understanding the dynamic behaviour of thePlasmodium falciparum metabolism during infection can help identify targets for drug development. In this Commentary, we highlight recently published studies in The FEBS Journal that cover mathematical modelling of glycolysis in P. falciparum and the identification and in vivo validation of metabolic drug targets.
 Free

Review Articles

Article Category
REVIEW ARTICLES

Vaccines against malaria—still a long way to go

Authors
Kai Matuschewski
First Published:
Vol:
284,
Pages:
2560–2568
DOI:
10.1111/febs.14107
image
Malaria is caused by Plasmodium parasites and remains the most important mosquito‐borne infectious disease. In this review, recent opportunities and persistent challenges for evidence‐based malaria vaccine design are discussed. A better understanding of Plasmodiumcell biology and immunology is essential to transform malaria into a vaccine‐preventable disease.
 Free
Article Category
REVIEW ARTICLES

Combating multidrug‐resistant Plasmodium falciparum malaria

Authors
Aung Myint Thu, Aung Pyae Phyo, Jordi Landier, Daniel M. Parker, François H. Nosten
First Published:
Vol:
284,
Pages:
2569–2578
DOI:
10.1111/febs.14127
image
Combating the spread of drug‐resistantPlasmodium falciparum requires a comprehensive approach. Modern information technology provides the means to detect, enumerate, map and monitor cases of malaria resistance and the foci of transmission. Early detection and treatment of clinical cases, detection of submicroscopic reservoirs and adapted vector control are the three pillars of a successful elimination.
 Open Access
Article Category
REVIEW ARTICLES

Oxidative stress in malaria and artemisinin combination therapy: Pros and Cons

Authors
Reginald A. Kavishe, Jan B. Koenderink, Michael Alifrangis
First Published:
Vol:
284,
Pages:
2579–2591
DOI:
10.1111/febs.14097
image
Malaria is characterized with oxidative stress derived from both the parasite's metabolism and the host immune response. Some antimalarial drugs increase oxidative stress. While oxidative stress can help eliminate parasites, it can also exacerbate the pathology. This article reviews oxidative stress in view of the current artemisinin‐based combination therapies in malaria.
 Free
Article Category
REVIEW ARTICLES

Unraveling the importance of the malaria parasite helicases

Authors
Renu Tuteja
First Published:
Vol:
284,
Pages:
2592–2603
DOI:
10.1111/febs.14109
image
Plasmodium falciparum contains nearly 5400 genes and a multistage life cycle in humans and mosquitoes. Helicases are ATP‐dependent nucleic acid unwinding enzymes. The P. falciparum genome analysis depicts that it contains some parasite‐specific helicases and homologs to most of the human helicases. Here, an overview of P. falciparum helicases and their importance in parasite growth and survival is presented.
 Free
Article Category
REVIEW ARTICLES

Proteases as antimalarial targets: strategies for genetic, chemical, and therapeutic validation

Authors
Edgar Deu
First Published:
Vol:
284,
Pages:
2604–2628
DOI:
10.1111/febs.14130
image
Proteases play a variety of biological functions in the malaria parasite. These include core biological processes such as protein homeostasis and traffic, but also parasite‐specific functions (haemoglobin degradation, parasite egress, red blood cell invasion). This review provides an overview about the role of proteases in parasite development and outlines chemical and genetic strategies to validate proteases as therapeutic targets.
 Open Access

Original Articles

Article Category
ORIGINAL ARTICLES

[Fe–S] cluster assembly in the apicoplast and its indispensability in mosquito stages of the malaria parasite

Authors
Manish Charan, Hadi Hasan Choudhary, Nidhi Singh, Mohammad Sadik, Mohammad Imran Siddiqi, Satish Mishra, Saman Habib
First Published:
Vol:
284,
Pages:
2629–2648
DOI:
10.1111/febs.14159
image
The sulfur mobilization (SUF) pathway of iron–sulfur [Fe–S] cluster assembly in the apicoplast of the malaria parasite has been delineated in this study. [4Fe–4S] clusters assembled on the SufBC2D complex are transferred to targets via either NfU or SufA. Conditional knockout of SufS, the first enzyme of the pathway, demonstrates its essentiality in sporozoite development in the mosquito, providing support for SUF as a potential intervention site.
Article Category
ORIGINAL ARTICLES

Lipid interactions modulate the structural and antigenic properties of the C‐terminal domain of the malaria antigen merozoite surface protein 2

Authors
Sreedam C. Das, Rodrigo A.V. Morales, Jeffrey Seow, Bankala Krishnarjuna, Ravindu Dissanayake, Robin F. Anders, Christopher A. MacRaild, Raymond S. Norton
First Published:
Vol:
284,
Pages:
2649–2662
DOI:
10.1111/febs.14135
image
MSP2 from the malaria parasite Plasmodium falciparum induces a protective immune response. Tethering the conserved C‐terminal region (MSP2172–221) to liposomes induced an antigenic state that was more similar to the parasite antigen. Lipid‐conjugated MSP2 may represent a useful vaccine formulation.
Article Category
ORIGINAL ARTICLES

A widened substrate selectivity filter of eukaryotic formate‐nitrite transporters enables high‐level lactate conductance

Authors
Marie Wiechert, Holger Erler, André Golldack, Eric Beitz
First Published:
Vol:
284,
Pages:
2663–2673
DOI:
10.1111/febs.14117
image
Formate‐nitrite transporters (FNT) contain a substrate selectivity filter based on a lysine in a hydrophobic environment (Φ/K). It is reminiscent of the aquaporin aromatic/arginine region regarding composition, function, and location within the protein. Eukaryotic FNTs conduct lactate due to a funnel‐shaped vestibule and a wide selectivity filter, whereas prokaryotic FNTs select for smaller substrates, mainly formate, nitrite, hydrosulfide, and acetate.
Article Category
ORIGINAL ARTICLES

Identification and characterization of ARS‐like sequences as putative origin(s) of replication in human malaria parasitePlasmodium falciparum

Authors
Meetu Agarwal, Krishanu Bhowmick, Kushal Shah, Annangarachari Krishnamachari, Suman Kumar Dhar
First Published:
Vol:
284,
Pages:
2674–2695
DOI:
10.1111/febs.14150
image
The eukaryotic genome replicates from multiple sites called origins. The genomic organization of these sites has been elusive in higher eukaryotes as well as in protozoan parasites. Here, we have identified and characterized the origins inPlasmodium falciparum by bioinformatic analysis and an experimental approach. An autocorrelation method was used to search for regions showing marked fluctuation or dips that may contain potential replication initiation sites. Finally the results of autocorrelation were verified experimentally.