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The article presents the papers that will be published in the forthcoming issues of the "British Journal of Haematology" including "The WHIM Syndrome Shows a Peculiar Dysgranulopoiesis: Myelokathexis," "Positron Emission Tomography Positive Distal Femur Following Fludarabine, Dexamethasone and Mitoxantrone Chemotherapy," "Optimal Haemophilia Care Versus the Reality," and "FQPD, A Novel Immunomodulatory Drug, Has Significant in Vitro Activity in Multiple Myeloma."

The oxazaphosphorine cyclophosphamide (CP) is a DNA-alkylating agent commonly used in cancer chemotherapy. This anticancer agent is administered as a prodrug activated by a liver cytochrome P450-catalyzed 4-hydroxylation reaction that yields the active, cytotoxic metabolite. The primary metabolite, 4-hydroxycyclophosphamide, equilibrates with the ring-open aldophosphamide that undergoes ß-elimination to yield the therapeutically active DNA cross-linking phosphoramide mustard and the byproduct acrolein. The present paper presents a DFT investigation of the different metabolic phases and an insight into the mechanism by which CP exerts its cytotoxic action. A detailed computational analysis of the energy profiles describing all the involved transformations and the mechanism of DNA alkylation is given with the aim to contribute to an increase of knowledge that, after more than 60 years of unsuccessful attempts, can lead to the design and development of a new generation of oxazaphosphorines. [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Authors. The authors have independently identified an error in the formula that was utilized to calculate the Quality Adjusted Life Years which invalidates the data and the conclusion of the paper. The authors have contacted the journal requesting to retract the article. Apologies are offered to the readers of the journal for any confusion or inconvenience that may have resulted from the publication of this article. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To recognise that assessing the competence of nurses delivering systemic anticancer therapy (SACT) is essential to ensure high-quality patient care • To learn about the development of a digital SACT competency passport that aims to improve learning experience and accessibility for users • To contribute towards revalidation as part of your 35 hours of CPD (UK readers) • To contribute towards your professional development and local registration renewal requirements (non-UK readers). Robust competency assessment of systemic anticancer therapy (SACT) nurses ensures high-quality care is delivered to patients. The UK Oncology Nursing Society (UKONS) developed the SACT competency passport to support training and assessment of SACT nurses. Used throughout the UK and the Republic of Ireland, the passport benefits staff, patients and employers. Limitations in terms of its accessibility and interactivity prompted UKONS to commission the creation of a digital version in the form of an app. This article introduces the app and discusses the features aiding the passport’s use. It also explains how to complete and mark the passport, how to assess others with it and how to provide feedback. Finally, the authors provide information about the implementation of the app and future developments. [ABSTRACT FROM AUTHOR]

Twelve (N^N^N)platinum pyridyl complexes, (N^N^N)Pt(pyF), were synthesised and investigated for their singlet oxygen generation and potential biological activities. They exhibited 1IL and 1MLCT absorption transitions at approximately 325 and 360 nm, identified through TD-DFT calculations. Luminescence was observed only in the L1-derived compounds in solution, with a dual emission with the main contribution of phosphorescence under deaerated conditions. Room temperature phosphorescence was detected in all solid-state cases. Electron-withdrawing substituents at specific positions (R1 and X) and the number of fluorine atoms in R2 were found to enhance the photosensitizing capabilities of these compounds. Biological assessments, including cytotoxicity and photocytotoxicity, were conducted to evaluate their potential as chemotherapeutic agents and photosensitizers. Complexes with chloro substitution in the N^N^N tridentate ligand of the central pyridine ring exhibited promising chemotherapeutic properties. Ancillary pyridine ring substitution became significant under irradiation conditions, with fluoromethylated substituents enhancing cytotoxicity. Complex 2-CF3 was the most efficient singlet oxygen producer and a highly effective photosensitizer. CHF2-substituted complexes also showed improved photosensitizing activity. DNA binding studies indicated moderate interactions with DNA, offering insights into potential biological applications. [ABSTRACT FROM AUTHOR]

Presents abstracts of papers invited for publication by the journal 'British Journal of Cancer.' Structure dynamics and energetic analysis of DNA and RNA in oligonucleotides; Advanced concepts of cancer chemotherapy using topoisomerase I; Significance of biophysics of drug binding for cancer agents.

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide and is known as "the king of cancers". Currently, gemcitabine (GEM) as the clinical drug of choice for chemotherapy of advanced pancreatic cancer has poor drug sensitivity and ineffective chemotherapy. Nardoguaianone L (G-6) is a novel guaiane-type sesquiterpenoid isolated from Nardostachys jatamansi DC., and it exhibits anti-tumor activity. Based on the newly discovered G-6 with anti-pancreatic cancer activity in our laboratory, this paper aimed to evaluate the potential value of the combination of G-6 and GEM in SW1990 cells, including cell viability, cell apoptosis, colony assay and tandem mass tags (TMT) marker-based proteomic technology. These results showed that G-6 combined with GEM significantly inhibited cell viability, and the effect was more obvious than that with single drug. In addition, the use of TMT marker-based proteomic technology demonstrated that the AGE-RAGE signaling pathway was activated after medication-combination. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays were used to validate the proteomic results. Finally, apoptosis was detected by flow cytometry. In conclusion, G-6 combined with GEM induced an increase in ROS level and a decrease in MMP in SW1990 cells through the AGE-RAGE signaling pathway, ultimately leading to apoptosis. G-6 improved the effect of GEM chemotherapy and may be used as a potential combination therapy for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Necroptosis plays an important role in the progression and metastasis of lung adenocarcinoma (LUAD) and regulates the inflammatory response and tumor microenvironment. First of all, through NRGs, we determined the LUAD early diagnosis model, which is composed of four necroptosis-related genes (NRGs) (AUC = 0.994), and the LUAD prognosis evaluation model, composed of nine NRGs (AUC = 0.826). Secondly, the LUAD prognosis model was found to be closely related to immune checkpoint inhibitor (ICI) treatment and chemosensitivity. ICI treatment is more suitable for low-risk patients, while chemotherapy is more effective for high-risk patients. Finally, we identified the core gene PANX1 for the first time, which is important for prognosis evaluation and early diagnosis, and analyzed its role in LUAD immunotherapy. This study provides a new target for the immunotherapy of LUAD and a new theoretical basis for future individualized treatment in the clinic. Necroptosis is a type of programmed necrosis that is different from apoptosis and necrosis. Lung cancer has the highest incidence and mortality worldwide, and lung adenocarcinoma is the most common subtype of lung cancer. However, the role of necroptosis in the occurrence and development of LUAD remains largely unexplored. In this paper, four NRGs and nine NRGs determined by big data analysis were used to effectively predict the risk of early LUAD (AUC = 0.994) and evaluate the prognostic effect on LUAD patients (AUC = 0.826). Meanwhile, ESTIMATE, single-sample gene set enrichment analysis (ssGSEA), genomic variation analysis (GSVA), gene set enrichment analysis (GSEA), and immune checkpoint analysis were used to explore the enrichment characteristics and immune research related to the prognostic model. In deep data mining, we were surprised to find that prognostic models also regulate the immune microenvironment, cell cycle, and DNA damage repair mechanisms. Thus, we demonstrated a significant correlation between model evaluation results, ICI treatment, and chemotherapeutic drug sensitivity. The low-risk population has a stronger tumor immune response, and the potential for ICI treatment is greater. People at high risk respond less to immunotherapy but respond well to chemotherapy drugs. In addition, PANX1, a core gene with important value in immune regulation, prognosis assessment, and early diagnosis, has been identified for the first time, which provides a new target for the immunotherapy of LUAD as well as a new theoretical basis for the basic research, clinical diagnosis, and individualized treatment of LUAD. [ABSTRACT FROM AUTHOR]

The mathematical study of the growth and treatment of cancer has been of great interest to researchers in the recent past as that can help clinical practitioners in adopting new treatment strategies to fight effectively against cancer. Although chemotherapy is the most common method of cancer treatment, the drug-resistant nature of tumor cells and the toxic effect of chemotherapeutic drugs on normal cells are major threats to the success of chemotherapy. In this paper, we propose a multi-drug chemotherapy model combined with an optimal control approach in which the amount of drugs is taken as control functions. The underlying mathematical model discusses the evolution of a heterogeneous tumor population and the dynamics of normal cells under chemotherapy. The model incorporates the pharmacokinetics of the anticancer agents as well. The proposed optimal control approach ensures maximum decay of the tumor cells while preserving a sufficient level of normal cells that would help faster recovery. [ABSTRACT FROM AUTHOR]

Simple Summary: Current cancer treatment strategies such as surgery, chemotherapy, and radiotherapy, have significant drawbacks. There is a need for a breakthrough approach to cancer treatment. Bacteriocin, an antimicrobial peptide, has shown several anticancer properties in vitro. Therefore, this article reviews the effect of bacteriocin on cancer cells and how bacteriocins affect cancer cells in vitro. This article aims to promote additional bacteriocin research, particularly in vivo studies, to fully understand the potential of bacteriocin as a cancer treatment agent. Cancer is regarded as one of the most common and leading causes of death. Despite the availability of conventional treatments against cancer cells, current treatments are not the optimal treatment for cancer as they possess the possibility of causing various unwanted side effects to the body. As a result, this prompts a search for an alternative treatment without exhibiting any additional side effects. One of the promising novel therapeutic candidates against cancer is an antimicrobial peptide produced by bacteria called bacteriocin. It is a non-toxic peptide that is reported to exhibit potency against cancer cell lines. Experimental studies have outlined the therapeutic potential of bacteriocin against various cancer cell lines. In this review article, the paper focuses on the various bacteriocins and their cytotoxic effects, mode of action and efficacies as therapeutic agents against various cancer cell lines. [ABSTRACT FROM AUTHOR]

This paper examines the effects of treatment on tumor‐immune dynamics based on a conceptual two‐dimensional model. In absence of treatment, this model exhibits regimes of "active" and "dormant" tumor. Increasing intensity of chemotherapy entails a significant complication of tumor‐immune interaction with parameter zones of monostability, bistability, and tristability where "active," "dormant," and "zero" tumor states can coexist. A detailed description of bifurcations, attractors, and their basins is given. Based on this mathematical analysis, we discuss efficiency of various programs of treatment combining chemotherapy and radiotherapy. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common type of cancer and it is treated with surgical intervention, radiotherapy, chemotherapy, or a combination of these regimens. Despite chemotherapy's ample use, it has limitations such as bioavailability, adverse side effects, high-dose requirements, low therapeutic indices, multiple drug resistance development, and non-specific targeting. Drug delivery vehicles or carriers, of which nanocarriers are prominent, have been introduced to overcome chemotherapy limitations. Nanocarriers have been preferentially used in breast cancer chemotherapy because of their role in protecting therapeutic agents from degradation, enabling efficient drug concentration in target cells or tissues, overcoming drug resistance, and their relatively small size. However, nanocarriers are affected by physiological barriers, bioavailability of transported drugs, and other factors. To resolve these issues, the use of external stimuli has been introduced, such as ultrasound, infrared light, thermal stimulation, microwaves, and X-rays. Recently, ultrasound-responsive nanocarriers have become popular because they are cost-effective, non-invasive, specific, tissue-penetrating, and deliver high drug concentrations to their target. In this paper, we review recent developments in ultrasound-guided nanocarriers for breast cancer chemotherapy, discuss the relevant challenges, and provide insights into future directions. [ABSTRACT FROM AUTHOR]

The mathematical study of cancer received great attention in recent years. The theoretical and numerical investigations of models employed for studying the growth of cancer cells and treatment of cancer can help the clinical practitioners in adapting new strategies to face the challenges posed by the deadly disease. Chemotherapy is the most common method of treatment for cancer. The resistance of tumor cells toward the administered drug and the toxic effect of anti-cancer agents on healthy cells are major hurdles to the success of therapy. In this paper, we study this as an optimal control problem in which the amount of drug injected is taken as control. The evolution of different types of cells — sensitive tumor cells, resistant tumor cells and normal cells — under treatment are analyzed. The pharmacokinetics of the drug is also incorporated into the mathematical model. We propose a treatment protocol that assures the death of a maximum number of tumor cells but also manages to keep the normal cells at a sufficient level. We also validated our theoretical results numerically. [ABSTRACT FROM AUTHOR]

Oncological pathologies take a toll on millions of lives throughout the world, with a burden set to spiral in the future. The humanity’s increasing lifespan has pushed physicists to come up with specific and improved methods of treatment, and even more so, aggressive, in order to fight back these cell degenerations. Chemotherapy remains still one of the most effective ways to treat cancer, but the price for health might be even higher than expected. The cognitive repercussions of cancer and its treatment have been under the spotlight for the past 20 years, where scientists focused on getting a deeper understanding of post-chemotherapy effects on the human brain. In this paper we dive into the psychological and psychiatric pathology linked to this treatment method, by examining a clinical case that envisions a resilient woman who overcame cancer, but still encountered some setbacks. [ABSTRACT FROM AUTHOR]

Tumor‐specific, hypoxia‐activated prodrugs have been developed to alleviate the side effects of chemotherapy drugs. However, the release efficiency of hypoxia‐activated prodrugs is restricted by the degree of tumor hypoxia, which further leads to poor cancer treatment effects. On the other hand, oxygen is consumed gradually in photodynamic therapy (PDT), which aggravates hypoxia at the tumor site. In this study, we combined hypoxia‐activated prodrugs with PDT agents to promote the prodrugs release, thereby improving their bioavailability and therapeutic effects. As a proof of concept, a mitochondria‐targeted molecular prodrug, CS‐P, was designed and synthesized. It can be selectively activated by tumor hypoxia to release chemotherapeutic drugs and photosensitizers, and then further discharge drugs after light irradiation. The design strategy proposed in this paper provides a new idea for enhancing hypoxia‐activated prodrug release and real‐time monitoring prodrug release. [ABSTRACT FROM AUTHOR]

The incidence of cancer is increasing today, particularly lung and chest cancer. Employing novel methods to detect cancer in its earliest stages and discover painless, noninvasive treatments are urgently needed. The goal of the proposed study is to investigate the value of automated breast volume scanning (ABUS) in conjunction with contrast-enhanced ultrasonography (CEUS) in properly diagnosing breast cancer in its early stages and the effectiveness of neoadjuvant chemotherapy (NAC) in treating the disease. For the research study, information on 98 patients who had NAC and surgery in the breast surgery department of the Shaanxi Provincial Cancer Hospital has been gathered. All patients have received four cycles of NAC and underwent conventional ultrasound (HUSS), CEUS, ABUS, and pathological examination. At the same time, receiver operating characteristic (ROC) curve analysis, single factor, multiple linear regression, and other methods have also been used to analyze the diagnostic efficacy of breast cancer and NAC efficacy evaluation results. The study of this paper is totally based on the data collected from Shaanxi Provincial Cancer Hospital. The statistical and computational analyses are performed on the data collected for drawing inferences. When the findings are compared to the results of the pathological examination, HUSS has demonstrated a significant distinction between benign and malignant diagnoses with a statistical value of P < 0.05.ABUS combined with CEUS has shown no considerable differences in correlation study. Except for negative likelihood ratio, the diagnostic performance indexes of CEUS+ ABUS are substantially higher than HHUS with P < 0.05. ROC curve analysis is also performed which shows that CEUS and ABUS combination has higher precision in the analysis of breast cancer. ABUS pooled with CEUS shows great application value in the judgment of breast cancer as per the results obtained from the statistical analysis on data of 98 patients. [ABSTRACT FROM AUTHOR]

Breast cancer continues to be the most diagnosed cancer among women worldwide. Neoadjuvant chemotherapy is the standard of care for breast cancer patients with locally advanced disease and patients with poor pathological features, such as triple-negative (TN) or human epidermal growth factor receptor-2 (HER2)-positive subtypes. Neoadjuvant therapy offers several advantages, including better surgical outcomes, early systemic treatment for micro-metastases, and accurate tumor biology and chemosensitivity assessment. Multiple studies have shown that achieving pathological complete response (pCR) following neoadjuvant chemotherapy is associated with better prognosis and better treatment outcomes; almost half of such patients may fail to achieve pCR. Tumor proliferative index, hormone receptor (HR) status, and HER2 expression are the major predictors of pCR. Strategies to improve pCR have been dependent on augmenting neoadjuvant chemotherapy with the addition of taxanes and dual anti-HER2 targeted therapy in patients with HER2-positive tumor, and more recently, immunotherapy for patients with TN disease. The clinical management of patients with residual disease following neoadjuvant chemotherapy varies and depends mostly on the level of HR expression and HER2 status. Recent data have suggested that switching trastuzumab to trastuzumab-emtansine (T-DM1) in patients with HER2-positive disease and the addition of capecitabine for patients with HER2-negative and HR-negative subtype is associated with a better outcome; both strategies are incorporated into current clinical practice guidelines. This paper reviews available and ongoing studies addressing strategies to better manage patients who continue to have residual disease following neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: To date, little and discordant data still exists on the management of cervical cancer (CC) during pregnancy. In this paper, we report our experience of the treatment of these patients analyzing the oncologic, obstetric, and neonatal outcomes. Methods: Between January 2010 and December 2021, 13 patients were diagnosed with CC during pregnancy. All patients underwent platinum-based neoadjuvant chemotherapy (NACT) and 11/13 patients underwent a cesarean radical hysterectomy (CRH). Results: All 13 patients were diagnosed with squamous-cell carcinoma, FIGO-2018 stage between IB2-IIIC1. The majority of patients had a partial (61.5%) or complete (15.4%) response to NACT. Most patients had a regular course of pregnancy and the obstetric complications observed were gestational diabetes mellitus in 23.1% and IUGR in 15.4% of cases. CRH was performed in the absence of major complications. Only 2 patients (15.4%) had disease recurrence and only 1 patient (7.7%) died of disease. All children are currently healthy. At birth, we observed mainly prematurity-related complications (38.5% respiratory distress syndrome and 7.7% neonatal jaundice) and only a case of congenital malformation (hypospadias). In our pediatric population, we reported a case of malignancy (acute myeloid leukemia). Conclusion: NACT seems to be safe and efficacious in controlling tumor burden during pregnancy. CRH following NACT appears to be feasible, avoiding repeated surgery and treatment delays. This approach is also reasonably safe from a maternal, obstetric, and neonatal point of view. [ABSTRACT FROM AUTHOR]

Materials & methodsA systematic literature review was conducted to critically examine patient selection for patients undergoing stereotactic body radiotherapy (SBRT) to the spine and pancreas on the CyberKnife robotic radiosurgical system (CK). Online databases were searched and data was collected and ranked using a system from the Scottish Intercollegiate Guideline Network. The quality of the evidence analysed was insufficient to generate universal recommendations. However, the conclusions reached do help to demonstrate the safety and efficacy of CK treatment to both pancreatic and spinal patients.ResultsExcellent local control rates and minimal acute toxicity were reported within the spinal literature with uncertainties remaining with regard to the precise tolerance of the spinal cord and the reliability of current toxicity prediction methods. For pancreatic patients prognosis remains dismal due to the tendency for patients to present with advanced or inoperable disease. Combinations of CK SBRT and Gemcitabine chemotherapy are given though regimes vary and overall survival is not extended due to the rapid onset of distant metastases. New chemotherapy agents are required as well as better means of predicting response to treatment.ConclusionNo randomised controlled trials or meta-analyses were identified in the review and these are required in order to generate universal guidelines [ABSTRACT FROM AUTHOR]

Electrochemotherapy is a new therapeutic option for patients with locally spread melanoma. It is based on the phenomenon of reversible electroporation, i.e. a transient increase in permeability of cell membranes under the influence of an appropriately modulated electric field. This allows multiplication of toxicity of a cytostatic agent entering the tumour cell. It is highly effective, especially in the palliative treatment of cancers located in the integument of the human body (skin and subcutaneous tissue). Available literature provides a mandate both for the application of this method in the aforementioned cases as well as for further work on its development. This paper focuses on reviewing the literature concerning the use of electrochemotherapy in the treatment of melanoma. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to assess the efficacy and safety of delivering intraperitoneal chemotherapy and cytoreductive surgery for peritoneal metastases coupled with curative treatment of colorectal liver metastases. Areas covered: A comprehensive literature search using PubMed was conducted to screen for eligible records. Studies evaluating colorectal surgery and intraperitoneal chemotherapy combined with curative treatment of liver metastases were included. We excluded duplicate publications. Sixty-seven full-text papers were assessed and six papers were finally included. The overall survival in the included studies ranged from 6–49 months. Five-year survival ranged from 18%-28%, three-year survival ranged from 22%-42% and two-year survival ranged from 34%-78%. Survival was lower in patients with liver metastases and peritoneal carcinomatosis (PC) than those with PC alone in the majority of studies. Expert commentary: This review poses questions rather than presenting answers. The heterogeneity of survival data suggests the possible benefit of this aggressive treatment approach in selected patients. Standardization of the technique used for intraperitoneal chemotherapy instillation, agent used as well as the systemic chemotherapy and targeted therapy type and duration through prospective controlled trials is required to provide an evidence of a higher strength to support or prohibit this treatment strategy. [ABSTRACT FROM PUBLISHER]

This review focuses on the role of cancer stem cells in tumor development and summarizes multiple therapeutic approaches based on them. Cancer research has been significant in medical research as it is increasingly recognised as a worldwide public health concern. Although modern medical treatment can be done utilizing chemotherapy or radiotherapy, tumors' high mortality and recurrence rate remain a critical issue. However, in recent years, based on a large number of studies on cancer, scientists have put forward the theory of cancer stem cells, aiming to provide prospective treatment theories and methods for cancer therapies. These innovative treatments have brought hope to a complete cure for cancer. This paper first reviews the current status of cancer development, the hot theory of cancer stem cells, and the role of cancer stem cells in curing cancer. Then, three popular cancer stem cell treatments are reviewed, briefly discussed, and analyzed. Finally, the prospect of a treatment system is examined based on cancer stem cells. [ABSTRACT FROM AUTHOR]

Cancer is the leading cause of death worldwide. Tumors consist of heterogeneous cell populations that have different biological properties. While conventional cancer therapy such as chemotherapy, radiotherapy, and surgery does not target cancer cells specifically, gene therapy is attracting increasing attention as an alternative capable of overcoming these limitations. With the advent of gene therapy, there is increasing interest in developing non-viral vectors for genetic material delivery in cancer therapy. Nanosystems, both organic and inorganic, are the most common non-viral vectors used in gene therapy. The most used organic vectors are polymeric and lipid-based delivery systems. These nanostructures are designed to bind and protect the genetic material, leading to high efficiency, prolonged gene expression, and low toxicity. Quality by Design (QbD) is a step-by-step approach that investigates all the factors that may affect the quality of the final product, leading to efficient pharmaceutical development. This paper aims to provide a new perspective regarding the use of the QbD approach for improving the quality of non-viral vectors for genetic material delivery and their application in cancer therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: In this paper we perform an introduction about pregnancy-associated cancer (PAC) and transplacental passage of antineoplastic agents. Furthermore, we describe therapeutic use and potential toxic effects of chemotherapeutic drug (alkylating agents, antimetabolites agents, anthracyclines, topoisomerase inhibitors, antimitotic agents, actinomycin-D, bleomycin) and targeted agents during pregnancy. This manuscript may be a useful and practical guide for the management of PAC, which is a challenge for clinicians that have to consider alike maternal benefits and fetal potential risks correlated to the antineoplastic treatment. The incidence of PAC is relatively infrequent among pregnant women. However, it has gradually increased in recent years, becoming a challenging area for clinicians that should take into account in the same way maternal benefits and fetal potential risks correlated to the antineoplastic treatment. None of the antineoplastic drugs is completely risk-free during the pregnancy, the timing of exposure and transplacental transfer properties influence the toxicity of the fetus. Despite the lack of guidelines about the management of PAC, several studies have described the use and the potential fetal and neonatal adverse events of antineoplastic drugs during pregnancy. We provide a review of the available literature about the transplacental passage and fetal effects of chemotherapy and targeted agents, to guide the clinicians in the most appropriate choices for the management of PAC. [ABSTRACT FROM AUTHOR]

Soil-transmitted helminth (STH) infections cause significant morbidity in children and women of reproductive age. The World Health Organization (WHO) recommends preventive chemotherapy (PC) of at-risk populations with anthelminthics to control these infections. Historically, STH are very intensively transmitted in Pemba Island (Zanzibar). A survey conducted in 1994 in 12 schools estimated a STH prevalence near to 100%. This extremely high prevalence induced the introduction of PC in the island; initially, however, PC was not regularly administered because of difficulties linked to drug procurement. A second STH survey, conducted in 2011, in 24 schools estimated a prevalence of STH of 89%; after this survey, PC was regularly administered until 2018. We conducted a survey in 2021 using the same method as that used in 2011. The prevalence of STH was evaluated at 80% (95% CI 78.1–81.5) and most of the STH cases were due to Trichuris trichiura. More than 32% (95% CI 30.3–34.0) of the children investigated had infections of moderate or heavy intensity. PC has been conducted for over 25 years in Pemba Island. However, despite its beneficial impact, both the prevalence and the intensity of STH infections remain high, and the intervention has been insufficient in controlling STH morbidity. This is probably due to a combination of irregular PC, climatic conditions favourable to STH transmission, the low sensitivity of T. trichiura to benzimidazoles, high population density and poor sanitation. Improvement of sanitation coverage remains a key measure to permanently reduce the prevalence and intensity of STH. Possible changes to the present PC approaches to better control STH in Pemba would be (i) to assure high coverage in all schools, (ii) to use mebendazole instead of albendazole given its better activity on T. trichiura and (iii) to use a combination of ivermectin and mebendazole to further increase anthelminthic efficacy on T. trichiura. Author summary: A survey conducted in 1994 in school aged children showed that soil-transmitted helminth were very intensively transmitted in Pemba Island (Zanzibar) with prevalence near to 100%. Between 1994 and 2011 several rounds of administration of anthelminthic were organized and a second survey was conducted in 2011 showing a decrease of prevalence and intensity of infection. The present paper reports the results of a third survey conducted in 2021 showing a further decline of the prevalence and a persistence of T. trichiura as the more prevalent parasite (in 1994 hookworms were the most transmitted STH). The interventions conducted until now where not sufficient to eliminate the morbidity caused by these parasites and it is suggested to include ivermectin in the anthelminthic distributed periodically. [ABSTRACT FROM AUTHOR]

The majority of patients with advanced, high-grade epithelial-tubo ovarian cancer (EOC) respond well to initial treatment with platinum-based chemotherapy; however, up to 80% of patients will experience a recurrence. Poly(ADP-ribose) Polymerase (PARP) inhibitors have been established as a standard of care maintenance therapy to prolong remission and prevent relapse following a response to first-line platinum-chemotherapy. Olaparib and niraparib are the PARP inhibitors currently approved for use in the first-line maintenance setting in Canada. Selection of maintenance therapy requires consideration of patient and tumour factors, presence of germline and somatic mutations, expected drug toxicity profile, and treatment access. This paper discusses the current clinical evidence for first-line PARP inhibitor maintenance therapy in patients with advanced, high-grade EOC and presents consensus statements and a treatment algorithm to aid Canadian oncologists on the selection and use of PARP inhibitors within the Canadian EOC treatment landscape. [ABSTRACT FROM AUTHOR]

Selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-loaded microspheres is increasingly used for the treatment of Intrahepatic Cholangiocarcinoma (ICC). Dosimetry verifications post-treatment are required for a valid assessment of any dose-response relationship. We performed a systematic review of the literature to determine how often clinics conducted post-treatment dosimetry verification to measure the actual radiation doses delivered to the tumor and to the normal liver in patients who underwent SIRT for ICC, and also to explore the corresponding dose-response relationship. We also investigated other factors that potentially affect treatment outcomes, including the type of microspheres used and concomitant chemotherapy. Out of the final 47 studies that entered our study, only four papers included post-treatment dosimetry studies after SIRT to quantitatively assess the radiation doses delivered. No study showed that one microsphere type provided a benefit over another, one study demonstrated better imaging-based response rates associated with the use of glass-based TheraSpheres, and two studies found similar toxicity profiles for different types of microspheres. Gemcitabine and cisplatin were the most common chemotherapeutic drugs for concomitant administration with SIRT. Future studies of SIRT for ICC should include dosimetry to optimize treatment planning and post-treatment radiation dosage measurements in order to reliably predict patient responses and liver toxicity. [ABSTRACT FROM AUTHOR]

Cancer is fundamentally a disease of aberrant genetics. In contrast to nonmalignant cells, cancer cells are not only able to tolerate these genetic insults but are in fact enabled by them. While cancer treatment has progressed significantly in the last century, many current medical treatments rely on general cytotoxicity for rapidly dividing cells, rather than inhibiting the specific genetic lesions that enable malignant transformation. One promising area is the development of inhibitors targeted towards DNA replication. By targeting core pathways mutated in cancer, DNA replication inhibitor therapies offer new avenues for cancer treatment that spare patients the worst side effects of cytotoxic chemotherapy. One such target is RECQ1, a human helicase that shows great promise in cancer treatment when targeted as an adjuvant to other replication-based chemotherapies. In addition to summarizing the role replication stress plays in carcinogenesis, this paper discusses a triple combination of RECQ1, PARP1, and TOP1 inhibitors. While aggressive, this approach may increase the efficacy of these existing cancer therapies. [ABSTRACT FROM AUTHOR]

Bladder cancer is one of the most common malignant tumors in urinary system. Intravesical chemotherapy is a common adjuvant therapy after transurethral resection of bladder tumors. However, it has several disadvantages such as low drug penetration rate, short residence time, unsustainable action and inability to release slowly, thus new drug delivery and new modalities in delivery carriers need to be continuously explored. Nano-drug delivery system is a novel way in treatment for bladder cancer that can increase the absorption rate and prolong the duration of drug, as well as sustain the action by controlling drug release. Currently, nano-drug delivery carriers mainly included liposomes, polymers, and inorganic materials. In this paper, we reveal current researches in nano-drug delivery system in bladder cancer intravesical chemotherapy by describing the applications and defects of liposomes, polymers and inorganic material nanocarriers, and provide a basis for the improvement of intravesical chemotherapy drugs in bladder cancer. [ABSTRACT FROM AUTHOR]

The conventional concept of using nanocarriers to deliver chemotherapeutic drugs has advanced to accommodate additional diagnostic capability. Nanotheranostic agents (NTA), combining both treatment and diagnostic tools, are an ideal example of engineering-health integration for cancer management. Owing to the diverse materials used to construct NTAs, their safety, effectiveness, and diagnostic accuracy could vary substantially. This systematic review consolidated current NTAs incorporating 5-fluorouracil and elucidated their toxicity, anticancer efficacy, and imaging capability. Medline and Embase databases were searched up to March 18, 2022. The search, selection, and extraction were performed by the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines to ensure completeness and reproducibility. Original research papers involving 5-fluorouracil in the preparation of nanoparticles which reported their efficacy, toxicity, and diagnostic capability in animal cancer models were recruited. The quality of included studies was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Nine studies were eligible for the systematic review. There was no significant toxicity reported based on animal weight and organ histology. Complete tumor remission was observed in several animal models using chemo-thermal ablation with NTAs, proving the enhancement of 5-fluorouracil efficacy. In terms of imaging performance, the time to achieve maximum tumor image intensity correlates with the presence of targeting ligand on NTAs. The NTAs, which are composed of tumor-targeting ligands, hold promises for further development. Based on the input of current NTA research on cancer, this review proposed a checklist of parameters to recommend researchers for their future NTA testing, especially in animal cancer studies. Systematic Review Registration : website, identifier registration number. [ABSTRACT FROM AUTHOR]

Background: Onchocerciasis elimination currently relies on repeated ivermectin-based preventive chemotherapy. Current World Health Organization's guidelines strongly recommend, though with low evidence of certainty, the use of Ov16 serology testing in children younger than 10 years old to assess whether mass drugs administration can be safely stopped. Therefore, more evidences are needed to support the use of this marker as sero-evaluation tool. This study aimed at determining the relationship between microfilaridermia and anti-Ov16 IgG4, and their variation according to age, gender and ivermectin intake history. Methodology: A cross-sectional survey was conducted in an area where ivermectin-based MDA has been implemented since more than 20 years. A questionnaire was used to record ivermectin intake history for the last 5 years. All volunteers aged ≥2 years were tested for microfilaridermia. IgG4 antibodies against Ov16 antigen were determined using the Standard Diagnostic Ov16 IgG4 ELISA kits and the recombinant anti-Ov16 AbD19432 antibodies. Prevalences, microfilaridermia counts and IgG4 concentrations were compared with regards to age, gender and history of ivermectin intake. Principal findings: The prevalence of skin microfilariae was 23.4% (95% CI: 23.4–30.8), whereas Ov16 seroprevalence was 53.2% (95% CI: 47.9–58.4). A moderate positive percentage agreement (50.4%) and a high negative percentage agreement (69.2%) was found between skin snip and Ov16 serology in the whole population, while in children aged <10 years, the agreements were higher (positive percentage agreement: 62.6%; negative percentage agreement: 83.5%). In addition, no associations were found between ivermectin intake, Mf counts and estimated IgG4 concentration of participants. Anti-Ov16 IgG4 were higher in individuals harboring microfilariae than their negative counterparts (p<0.0001), though a negative correlation was found between skin microfilarial counts and anti-Ov16 IgG4 levels (r = -0.2400; p = 0.03). No variation in microfilarial counts according to age and gender was observed. Though positively correlated with age (r = 0.4020; p<0.0001), IgG4 was significantly different between the different age classes (p<0.0001). Conclusion/Significance: Our results revealed moderate positive and negative agreements between parasitological and immunological parameters of onchocerciasis infection after several rounds MDA. Anti-Ov16 IgG4 levels increased with age but decreased with microfilarial counts, suggesting a variation of anti-Ov16 IgG4 as a result of constant exposure and accumulation of infection. This brings evidence sustaining the use of Ov16 serology in children as evaluation tool. However, additional investigations are needed to further reshape the appropriate age range among children aged <10 years old. Author summary: The elimination of onchocerciasis places high demands on monitoring and evaluation. The current WHO's guidelines recommend the use of serological test (ELISA) to determine the presence of IgG4 antibodies to the O. volvulus specific antigen Ov16 among children aged <10 years old, thought with low evidence of certainty. In this paper, we explored the relationship between anti-Ov16 IgG4 antibodies and microfilaridermia counts, and assessed their variation according to age, gender and history of ivermectin intake. Our findings revealed no variation of Mf count and IgG4 with ivermectin intake. However, we observed that anti-Ov16 IgG4 decrease with microfilaridermia counts, but an increasing trend was observed with age. This brings evidence sustaining the use of Ov16 serology testing as exposition marker in children younger than 10 years. However, children age 2 to 4 years seem to have a very low anti-Ov16 IgG4 concentration, this finding should be considered when defining the age class for seroprevalence evaluation. [ABSTRACT FROM AUTHOR]

With the continuous development of medical science and technology, the medical community's understanding of the disease is constantly updated, just as strategies for treating malignant tumors are constantly updated. New diagnoses, followup indicators, and treatment plan formulations need more evidence to be supported. To date, radical surgical resection is still the preferred treatment for advanced digestive system malignancies, and combination therapy including chemotherapy and targeted therapy before or after surgery is aimed at improving the prognosis and quality of life of patients. However, if tumor recurrence, metastasis, chemotherapy, and drug resistance to targeted agents after surgery prevent the achievement of the desired therapeutic effect, and if neoadjuvant chemotherapy and targeted therapy cannot reduce the staging of the tumor, surgery cannot be performed. These are huge problems that we face now and will continue to face for some time. Relevant scientific data and evidence have been produced to explain unsatisfactory efficacy, such as epithelial-mesenchymal transformation, the tumor microenvironment, extracellular matrix proteins, cancer-related fibroblasts, and other factors that may be related to tumor progression and poor therapeutic effects. An extracellular matrix protein, periostin (POSTN), influences the above factors and has received multidisciplinary attention. In this paper, periostin and digestive systemrelated tumors are reviewed, and the production, mechanism of action, drug resistance correlation analysis, and coping strategies of periostin are summarized to further understand its characteristics. This work provides evidence for potential therapeutic targets for digestive system tumors in the future. [ABSTRACT FROM AUTHOR]

The São Tomé e Príncipe government is committed to achieving neglected tropical disease (NTD) control and elimination as a public health problem by 2025. In 2014, the Ministry of Health led a national survey to determine the prevalence of soil-transmitted helminths (STHs) and schistosomiasis across the country. Following this survey, a preventive chemotherapy (PC) campaign with mebendazole and praziquantel reached 31 501 school-age children in 2015. A follow-up 2017 survey to determine the impact of the intervention showed success in controlling schistosomiasis, as no infections were found, but limited impact on STHs, with prevalence similar to pretreatment levels. The survey also investigated the prevalence of a third NTD, lymphatic filariasis (LF), which was found to be endemic in the country. Since then the Ministry of Health has developed the Strategic Plan for the Fight Against Neglected Tropical Diseases 2019–2025 and identified gaps to be addressed. This narrative review systematises the existing literature reporting on the epidemiology of NTDs for which there are PC programs in São Tomé e Príncipe. PubMed was searched for relevant papers that measured the prevalence of LF, schistosomiasis and STHs. Additionally, data provided by the Ministry of Health surveys were analysed. Finally, we discuss current NTD control, including the impact of the coronavirus disease 2019 pandemic and identify priorities for program strengthening and operational research. [ABSTRACT FROM AUTHOR]

It is more than sixty years since the era of modern photodynamic therapy (PDT) for cancer began. Enhanced selectivity for malignant cells with a reduced selectivity for non-malignant cells and good biocompatibility along with the limited occurrence of side effects are considered to be the most significant advantages of PDT in comparison with conventional therapeutic approaches, e.g., chemotherapy. The phenomenon of multidrug resistance, which is associated with drug efflux transporters, was originally identified in relation to the application of chemotherapy. Unfortunately, over the last thirty years, numerous papers have shown that many photosensitizers are the substrates of efflux transporters, significantly restricting the effectiveness of PDT. The concept of a dynamic nanoplatform offers a possible solution to minimize the multidrug resistance effect in cells affected by PDT. Indeed, recent findings have shown that the utilization of nanoparticles could significantly enhance the therapeutic efficacy of PDT. Additionally, multifunctional nanoplatforms could induce the synergistic effect of combined treatment regimens, such as PDT with chemotherapy. Moreover, the surface modifications that are associated with nanoparticle functionalization significantly improve the target potential of PDT or chemo-PDT in multidrug resistant and cancer stem cells. [ABSTRACT FROM AUTHOR]

Background: Intervention-generated inequalities are unintended variations in outcome that result from the organisation and delivery of health interventions. Socioeconomic inequalities in treatment may occur for some common cancers. Although the incidence and outcome of lung cancer varies with socioeconomic position (SEP), it is not known whether socioeconomic inequalities in treatment occur and how these might affect mortality. We conducted a systematic review and meta-analysis of existing research on socioeconomic inequalities in receipt of treatment for lung cancer. Methods and Findings: MEDLINE, EMBASE, and Scopus were searched up to September 2012 for cohort studies of participants with a primary diagnosis of lung cancer (ICD10 C33 or C34), where the outcome was receipt of treatment (rates or odds of receiving treatment) and where the outcome was reported by a measure of SEP. Forty-six papers met the inclusion criteria, and 23 of these papers were included in meta-analysis. Socioeconomic inequalities in receipt of lung cancer treatment were observed. Lower SEP was associated with a reduced likelihood of receiving any treatment (odds ratio [OR] = 0.79 [95% CI 0.73 to 0.86], p,0.001), surgery (OR = 0.68 [CI 0.63 to 0.75], p,0.001) and chemotherapy (OR = 0.82 [95% CI 0.72 to 0.93], p = 0.003), but not radiotherapy (OR = 0.99 [95% CI 0.86 to 1.14], p = 0.89), for lung cancer. The association remained when stage was taken into account for receipt of surgery, and was found in both universal and non-universal health care systems. Conclusions: Patients with lung cancer living in more socioeconomically deprived circumstances are less likely to receive any type of treatment, surgery, and chemotherapy. These inequalities cannot be accounted for by socioeconomic differences in stage at presentation or by differences in health care system. Further investigation is required to determine the patient, tumour, clinician, and system factors that may contribute to socioeconomic inequalities in receipt of lung cancer treatment. [ABSTRACT FROM AUTHOR]

Dear Editor Recently, with great interest, we read the paper "Efficacy of modified FOLFOX6 chemotherapy for patients with unresectable pseudomyxoma peritonei" from Chikashi Ishioka et al. [[1]]. References 1 Hiraide S, Komine K, Sato Y. Efficacy of modified FOLFOX6 chemotherapy for patients with unresectable pseudomyxoma peritonei. However, the authors declared that "this is the first case series of mFOLFOX6 in patients with unresectable pseudomyxoma peritonei and the first case series of systemic chemotherapy for Asian patients with unresectable pseudomyxoma peritonei". [Extracted from the article]

This is a highlight on the paper by Bonnet et al.: A Lock‐and‐Kill Anticancer Photoactivated Chemotherapy Agent. which constitutes an important step toward establishing photoactivated chemotherapy (PACT) as a widespread tool to treat different health issues, specially tumors. PACT can be a useful technique to deliver already tested drugs, where the effect of the desired molecule is directed only to its target after light irradiation, even in the cases in which it is difficult to achieve a precise delivery in the desired organ or tissue. Ruthenium‐polipyridyl caged‐compounds are near ideal devices to deliver a drug in that precise fashion, albeit they usually fail in revealing their actual location due to their weak light emission properties. The mentioned work introduces a simple and clever idea: the use of a covalently linked fluorophore to map the caged‐compounds in‐vivo distribution prior to the eventual irradiation to activate the chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To describe the theoretical, evidence-based and consumer-informed development of a smartphone self-management program aiming to support adherence to oral chemotherapy in adolescents and adults diagnosed with cancer. Methods: The design of the program followed two frameworks for the development and evaluation of mHealth interventions and was conducted in three steps: 1) conceptualization, which involved an extensive literature review and a scoping review that led to the identification of the behavioral change strategies in the program; 2) definition of features and structure, based on a formative study with end-users to explore their preferences about the structure and elements of the program; and 3) selection of program delivery technology, whereby available technology platforms were examined and the most suitable tool to deliver the program was selected. Results: Three main reasons for oral chemotherapy non-adherence were identified: forgetfulness, side-effects and poor knowledge about oral chemotherapy. Key behavior change strategies were also identified, namely, medication intake reminders and information about oral chemotherapy and managing side-effects. Based upon end-user feedback the method of delivery of these behavioral strategies that was deemed most appropriate was conventional text messages. The reminders were standard, short, text-only messages sent when each oral chemotherapy dose was due, one way (no need to reply) and addressed the end-users using their first name. Delivery of information about oral chemotherapy and side-effects was tailored to each individual's preferred frequency. Conclusion: The careful design process described in this paper may serve to inform the development of future mobile phone-based medication adherence-enhancing interventions for people with cancer. A trial to explore end-users acceptability of and satisfaction with the intervention is currently underway. Trial Registration: ACTRN12618001987257p. [ABSTRACT FROM AUTHOR]

Purpose. To present a comprehensive review of the literature data, published between 2000 and 2019 on the PubMed and Web of Science databases, in the field of the tumor microenvironment in hepatocellular carcinoma (HCC). All the data were combined with the personal experiences of the authors. Design. From 1002 representative papers, we selected 86 representative publications which included data on epithelial-to-mesenchymal transition (EMT), angiogenesis, cancer stem-like cells (CSCs), and molecular background of chemoresistance or resistance to radiotherapy. Results. Although the central event concerns activation of the Wnt/β-catenin pathway, other signal pathways, such as c-Met/HGF/Snail, Notch-1/NF-κB, TGF-β/SMAD, and basic fibroblast growth factor-related signaling, play a role in the EMT of HCC cells. This pathway is targeted by specific miRNAs and long noncoding RNAs, as explored in this paper. A central player in the tumor microenvironment proved to be the CSCs which can be marked by CD133, CD44, CD90, EpCAM, and CD105. CSCs can induce resistance to cytotoxic therapy or, alternatively, can be synthesized, de novo, after chemo- or radiotherapy, especially after transarterial chemoembolization- or radiofrequency ablation-induced hypoxia. The circulating tumor cells proved to have epithelial, intermediate, or mesenchymal features; their properties have a critical prognostic role. Conclusion. The metastatic pathway of HCC seems to be related to the Wnt- or, rather, TGFβ1-mediated inflammation-angiogenesis-EMT-CSCs crosstalk link. Molecular therapy should target this molecular axis controlling the HCC microenvironment. [ABSTRACT FROM AUTHOR]

Ru(II) polypyridine complexes which can undergo photo-induced ligand dissociation and subsequent DNA covalent binding may potentially serve as photoactivated chemotherapeutic (PACT) agents. In this paper, three fluorinated dppz ligand coordinated Ru(II) complexes (2–4) containing four monodentate pyridine ligands were studied. All complexes released one pyridine and covalently bound to DNA upon 470 nm irradiation. Compared with the parent complex [Ru(dppz)(py)4]2+ (1), 2–4 displayed enhanced phototoxicity but diminished dark cytotoxicity, more favorable for PACT application. Complex 3 is the most efficient one with IC50 values of about 8 μM toward HeLa and SKOV-3 cell lines, and also has a much higher IC50 value toward normal L-02 cells. Our results indicate that fluorination on the retaining ligand may be an efficient way to improve the drug activity of Ru(II) PACT agents. [ABSTRACT FROM AUTHOR]

Aims: Tumour deposits (TDs) are clusters of cancer cells in the soft tissue that are discontinuous from the primary tumour. In this review we are exploring their relevance for prognosis in patients with gastric cancer. Methods and results: A literature search was performed to identify studies providing data on TDs and prognosis in gastric cancer patients. Eight papers were included in the meta‐analysis, which was carried out in terms of risk ratios (RR) and hazard ratios (HR) with 95% confidence interval (95% CI). Of 7445 patients, 1551 had TDs (20.9%). TDs were associated with a decreased overall survival (OS) in univariate (HR = 2.82, 95% CI = 1.9–4.3) and multivariate analyses (HR = 1.65, 95% CI = 1.3–2.1). TDs were also associated with known prognostic factors such as synchronous metastatic disease (RR = 9.5), invasion depth (RR = 1.8), lymph node metastasis (RR = 1.7), lymphatic invasion (RR = 1.7), vascular invasion (RR = 2.6) and poor differentiation (RR = 1.2). Conclusions: We found a strong indication that TDs are independent predictors of prognosis in patients with gastric cancer; hence, TDs should be included in the staging of gastric cancers. [ABSTRACT FROM AUTHOR]