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A solution approach is proposed for the interday problem of assigning chemotherapy sessions at a network of treatment centres with the goal of increasing the cost-efficiency of system-wide capacity use. This network-based scheduling procedure is subject to the condition that both the first and last sessions of a patient's treatment protocol are administered at the same centre the patient is referred to by their oncologist. All intermediate sessions may be administered at other centres. It provides a systematic way of identifying effective multi-appointment scheduling policies that exploit the total capacity of a networked system, allowing patients to be treated at centres other than their home centre. The problem is modelled as a Markov decision process which is then solved approximately using techniques of approximate dynamic programming. The benefits of the approach are evaluated and compared through simulation with the existing manual scheduling procedures at two treatment centres in Santiago, Chile. The results suggest that the approach would obtain a 20% reduction in operating costs for the whole system and cut existing first-session waiting times by half. A key conclusion, however, is that a network-based scheduling procedure brings no real benefits if it is not implemented in conjunction with a proactive assignment policy like the one proposed in this paper. [ABSTRACT FROM AUTHOR]

Chemotherapy scheduling at cancer treatment centres is a complex problem due to high and growing demand, diversity of treatment protocols, limitations on resources and the need to coordinate treatment session times with laboratory preparation of medication. Over a given planning horizon, treatment centres assign patients first to specific days (interday scheduling) and then to specific times within each day (intraday scheduling), the latter process including the definition of medication preparation time. This paper addresses the intraday scheduling problem using an integer programming model that attempts to schedule all patients assigned to the horizon, and the preparation of the medication to be administered, simultaneously. The linear relaxation of the model formulation, which is based on treatment patterns, is solved using column generation. The proposed approach allows for medication preparation on the day of treatment or a previous day subject to time slot availability. A case study is conducted using actual data from a Chilean cancer centre to compare through simulation the schedules generated by the proposed approach and the centre's manual method. The results show that the proposed approach performs better on makespan, treatment chair occupancy, number of overtime hours and finding solutions at high demand levels. [ABSTRACT FROM AUTHOR]

This paper deals with the robust state feedback stabilizability problem of linear time-invariant (LTI) systems in the presenceof polytopic uncertainty. The paper contributes two major results involving (i) necessary and sufficient conditions to simultaneouslycheck positivity and robust stability of an uncertain LTI system (ii) the development of a design algorithm to solve the mainstabilizability problem. This problem is not easy to deal with because it is not a convex problem. To cope with this issue, a designalgorithm is proposed that checks the design space of the stabilizer parameters, divides it into smaller subspaces, checks thefeasibility of the corner points of the design subspaces, removes the detected total infeasible design subspaces, and shrinks theremaining parts to solve the design problem, iteratively. The proposed algorithm is applied to the cancer chemotherapy applicationand the results demonstrate its efficacy to control the model considering the positivity condition. [ABSTRACT FROM AUTHOR]

Leishmaniasis, an infectious disease, manifests itself mostly in two forms, cutaneous leishmaniasis (CL) and, a more severe and potentially deadly form, visceral leishmaniasis (VL). The current control strategy for leishmaniasis relies on chemotherapy drugs such as sodium antimony gluconate (SAG) and meglumine antimoniate (MA). However, all these chemotherapy compounds have poor efficacy, and they are associated with toxicity and other adverse effects, as well as drug resistance. While research in vaccine development for leishmaniasis is continuously progressing, no vaccine is currently available. However, some experimental vaccines such as LEISH-F1+MPL-SE (V) have demonstrated some efficacy when used as drugs for CL patients. In this paper we use a mathematical model to address the following question: To what extent vaccine shots can enhance the efficacy of standard chemotherapy treatment of leishmaniasis? Starting with standard MA treatment of leishmaniasis and combining it with three injections of V , we find, by Day 84, that efficacy increased from 29% to 65–91% depending on the amount of the vaccine. With two or just one injection of V , efficacy is still very high, but there is a definite resurgence of the disease by end-time. [ABSTRACT FROM AUTHOR]

Dose optimization is a critical challenge in drug development. Historically, dose determination in oncology has followed a divergent path from other non-oncology therapeutic areas due to the unique characteristics and requirements in Oncology. However, with the emergence of new drug modalities and mechanisms of drugs in oncology, such as immune therapies, radiopharmaceuticals, targeted therapies, cytostatic agents, and others, the dose-response relationship for efficacy and toxicity could be vastly varied compared to the cytotoxic chemotherapies. The doses below the MTD may demonstrate similar efficacy to the MTD with an improved tolerability profile, resembling what is commonly observed in non-oncology treatments. Hence, alternate strategies for dose optimization are required for new modalities in oncology drug development. This paper delves into the historical evolution of dose finding methods from non-oncology to oncology, highlighting examples and summarizing the underlying drivers of change. Subsequently, a practical framework and guidance are provided to illustrate how dose optimization can be incorporated into various stages of the development program. We provide the following general recommendations: 1) The objective for phase I is to identify a dose range rather than a single MTD dose for subsequent development to better characterize the safety and tolerability profile within the dose range. 2) At least two doses separable by PK are recommended for dose optimization in phase II. 3) Ideally, dose optimization should be performed before launching the confirmatory study. Nevertheless, innovative designs such as seamless II/III design can be implemented for dose selection and may accelerate the drug development program. [ABSTRACT FROM AUTHOR]

Metastasis, the spread of cancer cells from a primary tumor to secondary location(s) in the human organism, is the ultimate cause of death for the majority of cancer patients. Although studied for more than 180 years, increasing efforts in recent years have significantly contributed to a better understanding of this aspect of tumor development. Adding to this understanding, our current paper proposes a multi-type branching process model, through which various topics, such as extinction of cancer cell clones, occurrence of successful mutants, and immediate risk of escaping extinction, are investigated. More specifically, the relationship between the lifespan distribution of cancer cells with subcritical reproduction and the waiting time until the occurrence of a mutant (having supercritical reproduction) cancer cell, escaping extinction, is highlighted. The theoretical studies formulated in this paper may allow our model to be tailored to real data available for particular kinds of cancer and chemotherapy. [ABSTRACT FROM AUTHOR]

This paper studies the integrated scheduling of consultation and treatment appointments for chemotherapy patients, while taking into account the stochastic duration of injection. Patients may require one or both types of consultation and treatment appointments. The objective is to minimize the clinic's overtime and the waiting time of patients in the clinic. To formulate the problem, we develop two two-stage stochastic programming models. We also propose a sample average approximation algorithm as the solution method. To improve the efficiency of our solution approach, we devise a specialized algorithm that quickly evaluates a given first-stage solution for a large set of scenarios, without solving the second-stage models. Several computational experiments are carried out to evaluate the performance of proposed models and algorithms. [ABSTRACT FROM AUTHOR]

In this paper, we have considered a tumour-immune model with the dosage effect of the targeted chemotherapeutic drug and its efficacy. The chemotherapeutic drug efficacy is characterized via way of means of its impact on the abnormal size of beginning tumours. In pharmacology, the effectiveness of a drug is a very important factor in developing a dosage for any disease. With these points of view regarding drug efficacy, we present a four compartmental mathematical model, viz, the population of tumour cells, T (t) , CD8 T-killer cells, E k (t) , CD4 T-helper cells, E h (t) , and the amount of targeted chemotherapeutic drug, C (t) , in the bloodstream, at any time t. A qualitative analysis of the proposed model, including the existence and boundedness of the model has been described here. The dynamics of the system are presented by examining the admissibility and stability of the system at trivial, dead, tumour-free, and co-existing equilibrium points with their respective biological significance. The conditions for the local stability of all equilibrium points are derived by using the Jacobian matrix and Routh–Hurwitz's criterion. Numerical calculations have been performed using the Multi-step Differential Transformation Method (Ms-DTM), and are presented and discussed briefly in terms of graphs. We have expressed that the model is suitable for the tumour removal with the passage of time, regardless of the initial population or tumour size. Also, the amount the dosage of the drug with an assigned numerical value for its efficacy is one of the important factors in the treatment. The efficacy term is included to see the effect of drug dosages in CD8 T-killer cells and CD4 T-helper cells compartment. [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]

According to the Centers for Disease Control and Prevention each year about 650,000 Americans with cancer undergo potentially lifesaving treatments usually via some combination of chemotherapeutic agents, adjuvants, or hormones. Over one hundred thousand of these patients are likely subsequently to experience difficulties with concentration and memory. These deficits may last for several months or persist for years. This paper surveys key components of the chemobrain story: Demographics; deficits, drugs, coping strategies, and the possibilities for recovery. [ABSTRACT FROM AUTHOR]

In this paper, a kind of pH-responsive mesoporous silica targeted drug delivery system (DOX-loaded N-CQDs/HA gated pSiO2/MPEG-Glu) was designed and synthesised. In this system, active mesoporous silica (pSiO2) worked as a carrier material, methoxy polyethene glycol amine (MPEG) and L-glutamic acid (Glu) can be coupled and grafted to the surface of the pSiO2 drug carrier to improve the stability of the drug delivery system, nitrogen-doped carbon quantum dots (N-CQDs) and hyaluronic acid (HA) can inhibit the rapid release of drug. Ultraviolet (UV-Vis) spectrum showed that the drug-loading rate of DOX is 8.9%, the drug release in vitro study suggested that the prepared silica drug delivery system had significant pH-responsive and targeted DOX release, the drug release rate is 55.7% at pH = 5.0, which was much higher than the release of pH = 7.4; CLSM and MTT showed that the drug delivery system can enter into cancer cells through endocytosis and the DOX can act on cell nucleus, exhibiting a targeted therapy on cancer cells. [ABSTRACT FROM AUTHOR]

In this article the author focuses on the importance of health literacy in an organization. The author states that there are many problems surrounds low health literacy like managing chronic illness, increased chances of experiencing serious medication errors, difficulty communicating with health providers. The author further mentions the roundtable discussion by the Institute of Medicine (IOM) on Health Literacy that found 18 attributes of a health literate health care organization including establish promoting health literacy as an organizational responsibility.

The pharmacological treatment of cancer has evolved from cytotoxic to molecular targeted therapy. The median survival gains of 124 drugs approved by the FDA from 2003 to 2021 is 2.8 months. Targeted therapy is based on the somatic mutation theory, which has some paradoxes and limitations. While efforts of targeted therapy must continue, we must study newer approaches that could advance therapy and affordability for patients. This work briefly overviews how cancer therapy has evolved from cytotoxic chemotherapy to current molecular-targeted therapy. The limitations of the one-target, one-drug approach considering cancer as a robust system and the basis for multitargeting approach with polypharmacotherapy using repurposing drugs. Multitargeted polypharmacotherapy for cancer with repurposed drugs should be systematically investigated in preclinical and clinical studies. Remarkably, most of these proposed drugs already have a long history in the clinical setting, and their safety is known. In principle, the risk of their simultaneous administration should not be greater than that of a first-in-human phase I study as long as the protocol is developed with strict vigilance to detect early possible side effects from their potential interactions. Research on cancer therapy should go beyond the prevailing paradigm targeted therapy. [ABSTRACT FROM AUTHOR]

This study aimed to assess the efficacy and safety of FOLFIRI and paclitaxel in patients with advanced gastric cancer (AGC) who were previously treated with first-line modified docetaxel, cisplatin, 5-fluorouracil (mDCF), or 5-fluorouracil, oxaliplatin, docetaxel (FLOT). Patients who received a triplet regimen in the first line setting and were treated with FOLFIRI or paclitaxel in the second-line treatment were included. The study included 198 patients, with 115 receiving FOLFIRI and 83 receiving paclitaxel. The median age was 58 (range = 24–69). The median progression-free survival (mPFS) was 5.2 [95% confidence interval (CI) = 4.4–5.5] months in the FOLFIRI arm, and 4.1 (95% CI = 3.3–4.6) months in the paclitaxel arm (p =.007). The median overall survival (mOS) was 9.4 (95% CI = 7.4–10.5) months in the FOLFIRI arm and 7.2 (95% CI = 5.6–8.3) months in the paclitaxel arm (p =.008). Grade 3–4 neuropathy was higher in patients receiving paclitaxel compared to those receiving FOLFIRI (p =.04). Grade 3–4 diarrhea was 8% in the FOLFIRI arm and 2.4% in the paclitaxel arm (p =.02). Beyond progression with docetaxel-based triplet chemotherapy, FOLFIRI may be preferred as a second-line treatment over paclitaxel due to its longer mPFS and mOS. [ABSTRACT FROM AUTHOR]

Health services provided at home are becoming more important in most European countries. A better understanding of the specificities of home care (HC) operations and their management is therefore necessary. The importance of operations management for HC is obvious; such systems are faced with a growing demand for care and higher expectations for improved service delivery with more and more constraints on available budget and resources. Based on interviews of HC practices in France and Italy as well as an international review of the literature related to HC operations, this paper aims at contributing to a better characterisation of HC operations and the associated decision-making models. The main part of the presentation is made at a generic level and the paper includes also a more specific part on the chemotherapy at home process. We also provide a discussion on the most relevant research topics in the field of HC operations management. [ABSTRACT FROM PUBLISHER]

Combination chemotherapy is widely exploited for suppressing drug resistance and achieving synergistic anticancer efficacy in the clinic. In this paper, the nanostructured targeting methotrexate (MTX) plus pemetrexed (PMX) chitosan nanoparticles (CNPs) were developed by modifying methoxy polye (thylene glycol) (mPEG), in which PEGylation CNPs was used as stealth nanocarriers (PCNPs) and MTX was employed as a targeting ligand and chemotherapeutic agent as well. Studies were undertaken on human lung adenocarcinoma epithelial (A549) and Lewis lung carcinoma (LLC) cell lines, revealing the anti-tumor efficacy of nanoparticle drug delivery system. The co-delivery nanoparticles (MTX-PMX-PCNPs) had well-dispersed with sustained release behavior. Cell counting kit-8 (CCK8) has been used to measure A549 cell viability and the research showed that MTX-PMX-PCNPs were much more effective than free drugs when it came to the inhibition of growth and proliferation. Cell cycle assay by flow cytometry manifested that the MTX-PMX-PCNPs exhibited stronger intracellular taken up ability than free drugs at the same concentration. In vivo anticancer effect results indicated that MTX-PMX-PCNPs exhibited a significantly prolong blood circulation, more tumoral location accumulation, and resulted in a robust synergistic anticancer efficacy in lung cancer in mice. The results clearly demonstrated that such unique synergistic anticancer efficacy of co-delivery of MTX and PMX via stealth nanocarriers, providing a prospective strategy for lung cancer treatment. [ABSTRACT FROM AUTHOR]

How to overcome drug resistance and prevent tumor metastasis is key to the success of malignant tumor therapy. In this paper, ADH-1 peptide-modified liposomes (A-LP) have been successfully constructed for restoring chemosensitivity and suppressing cancer cell migration. With a particle size of about 90 nm, this functionalized nanocarrier was loaded with fluorescent probe or paclitaxel (PTX). Cellular uptake studies showed that A-LP facilitated the delivery of anticancer drug to tumor cells undergoing EMT. Interestingly, this nanocarrier enhanced chemosensitivity by assessing the cell activity using CCK-8 assay. Further, the results of Wound scratch assay and Transwell migration assay showed the inhibition effect of this nanocarrier on tumor cell migration. Moreover, this nanocarrier exhibited significant tumor-targeting ability and anti-tumor efficacy in vivo. Collectively, A-LP might be a novel targeted drug delivery system to enhance the efficacy of chemotherapy and prevent tumor metastasis. [ABSTRACT FROM AUTHOR]

Background: Locoregional hyperthermia is applied to deep-seated tumours in the pelvic region. Two very different heating techniques are often applied: capacitive and radiative heating. In this paper, numerical simulations are applied to compare the performance of both techniques in heating of deep-seated tumours. Methods: Phantom simulations were performed for small (30 × 20 × 50 cm3) and large (45 × 30 × 50 cm3), homogeneous fatless and inhomogeneous fat-muscle, tissue-equivalent phantoms with a central or eccentric target region. Radiative heating was simulated with the 70 MHz AMC-4 system and capacitive heating was simulated at 13.56 MHz. Simulations were performed for small fatless, small (i.e. fat layer typically <2 cm) and large (i.e. fat layer typically >3 cm) patients with cervix, prostate, bladder and rectum cancer. Temperature distributions were simulated using constant hyperthermic-level perfusion values with tissue constraints of 44 °C and compared for both heating techniques. Results: For the small homogeneous phantom, similar target heating was predicted with radiative and capacitive heating. For the large homogeneous phantom, most effective target heating was predicted with capacitive heating. For inhomogeneous phantoms, hot spots in the fat layer limit adequate capacitive heating, and simulated target temperatures with radiative heating were 2-4 °C higher. Patient simulations predicted therapeutic target temperatures with capacitive heating for fatless patients, but radiative heating was more robust for all tumour sites and patient sizes, yielding target temperatures 1-3 °C higher than those predicted for capacitive heating. Conclusion: Generally, radiative locoregional heating yields more favourable simulated temperature distributions for deep-seated pelvic tumours, compared with capacitive heating. Therapeutic temperatures are predicted for capacitive heating in patients with (almost) no fat. [ABSTRACT FROM AUTHOR]

Percutaneous ethanol injection (PEI) therapy was used in liver cancer treatment, however, the therapeutic ethanol in PEI easily flew away from injected solid tumours and hinder the treatment effect. In this paper, injectable supramolecular gels formed by self-assembly of low molecular weight gelators (LMWGs) based on glycylglycine modified phenylboronic acid were prepared to localize ethanol and load chemotherapeutic drug for in situ synergistic therapy. The mechanism, morphology and rheological property of supramolecular gels were characterized by NMR, UV, SEM, etc. The rheological study revealed that the gels were formed in situ rapidly and recovered promptly once damaged. The gels were non-toxicity to both normal 3T3 fibroblasts cells and 4T1 breast cancer cells. Doxorubicin (DOX) hydrochloride and ethanol were encapsulated in the gels for the combination of chemotherapy and PEI therapy. The in vivo anticancer activity of the DOX-loaded gels was carried out in tumour bearing mice. The injected gels were coated around tumour tissues to lock ethanol, and DOX was released sustainingly from the gels to maintain effective concentration to induce the apoptosis of tumour cells. DOX-loaded gels and the ethanol exhibited excellent therapeutic efficacy and low side effects in local cancer therapy. [ABSTRACT FROM AUTHOR]

Glioma is the most common primary malignant brain tumour and the effect of chemotherapy is hampered by low permeability across the blood–brain-barrier (BBB). Borneol is a time-honoured ‘Guide’ drug in traditional Chinese medicine and has been proved to be capable of promoting free drugs into the brain efficiently, but there are still risks that free drugs, especially anti-glioma drugs, may be disassembled and metabolised before penetrating the BBB and caused the whole brain distribution. The purpose of this paper was to investigate whether borneol intervention could facilitate the BBB penetration and assist glioma treatment by combining with doxorubicin (DOX) loaded PAMAM dendrimers drug delivery system modified with Angiopep-2 (a ligand of the low-density lipoprotein receptor-related protein, which overexpress both in the BBB and gliomas). The results demonstrated that Angiopep-2 modification could actually enhance the affinity between the dendrimers and the targeting cells and finally increase the cell uptake and boost the anti-tumour ability. Borneol physical combination could further enhance the anti-tumour efficiency of this targeting drug delivery system (TDDS) after penetrating BBB. Compared with free DOX solution, this TDDS illustrated obviously sustained and pH-dependent drug release. This suggested that this synergetic strategy provided a promising way for glioma therapy. [ABSTRACT FROM PUBLISHER]

Despite the evidence that photodynamic therapy (PDT) associated with chemotherapy presents great potential to overcome the limitations of monotherapy, little is known about the current status of this combination against cervical cancer. This systematic review aimed to address the currently available advances in combining PDT and chemotherapy in different research models and clinical trials of cervical cancer. We conducted a systematic review based on PRISMA Statement and Open Science Framework review protocol using PubMed, Web of Science, Embase, Scopus, LILACS, and Cochrane databases. We selected original articles focusing on 'Uterine Cervical Neoplasms' and 'Photochemotherapy and Chemotherapy' published in the last 10 years. The risk of bias in the studies was assessed using the CONSORT and SYRCLE tools. Twenty-three original articles were included, focusing on HeLa cells, derived from endocervical adenocarcinoma and on combinations of several chemotherapeutics. Most of the combinations used modern drug delivery systems for improved simultaneous delivery and presented promising results with increased cytotoxicity compared to monotherapy. Despite the scarcity of animal studies and the absence of clinical studies, the combination of chemotherapy with PDT presents a potential option for cervical cancer therapy requiring additional studies. [ABSTRACT FROM AUTHOR]

This paper explores the connection between paclitaxel, a chemotherapeutic agent, and gastric cancer cells. In this experiment, it is demonstrated that paclitaxel triggers autophagy and inhibits proliferation of gastric cancer cells. An 3–(4,5–dimethyl–2–thiazolyl)–2,5–diphenyl–2–H–tetrazolium bromide (MTT) assay was used to detect cell viability and the IC50of paclitaxel. Western blot was used to detect the expression levels of P62, and to measure the protein expression of autophagy. Immunofluorescence was used to reveal the appearance of punctate structures in the cytoplasm—this ultrastructure associated with autophagy was observed by microscopy. Electron microscopy revealed the formation of double-membrane autophagosomes, a typical structure of autophagy. In conclusion, our research indicates that paclitaxel may influence gastric cancer BGC823 cells by way of inducing autophagy. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is a neoplastic disorder of mature B lymphocytes. While traditionally treated with combinations of chemoimmunotherapy, the therapeutic options for CLL have expanded in recent years with the emergence of novel oral agents, such as the Bruton tyrosine kinase inhibitor ibrutinib, that are well tolerated and highly efficacious. The role of novel agents in the first-line setting is now being investigated in head-to-head clinical trials. In this discussion paper, we consider the role of novel agents in the up-front setting, using three case studies of treatment-naive patients to highlight how choice of therapy may be individualized depending on the characteristics of the patient and the disease, as well as patient preferences. [ABSTRACT FROM PUBLISHER]

Diagnosis and treatment of lung cancer have been characterized with a variety of challenges. However, with the advancement in magnetic nanoparticle (MNP) technology, many challenges in the diagnosis and treatment of lung cancer are on the decline. The MNPs have led to many break-through in cancer therapy. This paper seeks to establish the role of MNPs in diagnosis and treatment of lung cancer. It proposes that the existing challenges in the diagnosis and treatment of lung cancer can be addressed through application of MNPs in the process. [ABSTRACT FROM AUTHOR]

The article presents the authors views on the benefits of open access for articles published in the journal. The author also mentions the growth in scientific articles published by the journal. It also mentions the journals focus on scientific disciplines such as cold therapy, chemotherapy, and tumor immunology.

Pancreas ductal adenocarcinoma (PDAC) is a frequently lethal malignancy that poses unique therapeutic challenges. The current mainstay of therapy for metastatic PDAC (mPDAC) is cytotoxic chemotherapy. NALIRIFOX (liposomal irinotecan, fluorouracil, leucovorin, oxaliplatin) is an emerging standard of care in the metastatic setting. An evolving understanding of PDAC pathogenesis is driving a shift toward targeted therapy. Olaparib, a poly-ADP-ribose polymerase (PARP) inhibitor, has regulatory approval for maintenance therapy in BRCA-mutated mPDAC along with other targeted agents receiving disease-agnostic approvals including for PDAC with rare fusions and mismatch repair deficiency. Ongoing research continues to identify and evaluate an expanding array of targeted therapies for PDAC. This review provides a brief overview of standard therapies for PDAC and an emphasis on current and emerging targeted therapies. There is notable potential for targeted therapies for KRAS-mutated PDAC with opportunity for meaningful benefit for a sizable portion of patients with this disease. Further, emerging approaches are focused on novel immune, tumor microenvironment, and synthetic lethality strategies. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most lethal cancers. Single-cell RNA sequencing (scRNA-seq) and protein-protein interactions (PPIs) have enabled the systematic study of CRC. In our research, the activation of the AKT pathway in CRC was analyzed by KEGG using single-cell sequencing data from the GSE144735 dataset. The correlation and PPIs of MDFI and ITGB4/LAMB3 were examined. The results were verified in the TCGA and CCLE and further tested by coimmunoprecipitation experiments. The effect of MDFI on the AKT pathway via ITGB4/LAMB3 was validated by knockdown and lentiviral overexpression experiments. The effect of MDFI on oxaliplatin/fluorouracil sensitivity was probed by colony formation assay and CCK8 assay. We discovered that MDFI was positively associated with ITGB4/LAMB3. In addition, MDFI was negatively associated with oxaliplatin/fluorouracil sensitivity. MDFI upregulated the AKT pathway by directly interacting with LAMB3 and ITGB4 in CRC cells, and enhanced the proliferation of CRC cells via the AKT pathway. Finally, MDFI reduced the sensitivity of CRC cells to oxaliplatin and fluorouracil. In conclusion, MDFI promotes the proliferation and tolerance to chemotherapy of colorectal cancer cells, partially through the activation of the AKT signaling pathway by the binding to ITGB4/LAMB3. Our findings provide a possible molecular target for CRC therapy. [ABSTRACT FROM AUTHOR]

Context:Glioblastoma multiforme (GBM) is by far the most common and aggressive form of glial tumor. It is characterized by a highly proliferative population of cells that invade surrounding tissue and that frequently recur after surgical resection and chemotherapy. Over the last decades, a number of promising novel pharmacological approaches have been investigated, but most of them have failed clinical trials due to some side-effects such as toxicity and poor drug delivery to the brain. The major obstacle in the treatment of GBM is the presence of the blood–brain barrier (BBB). Due to their relatively high molecular weight, most therapeutic drugs fail to cross the BBB from the blood circulation.Objective:This paper sheds light on the characteristics of GBM and the challenges of current pharmacological treatments. A closer look is given to the role of nanotechnology in the field of drug delivery, and its application in the treatment of brain tumors such as GBM.Method:For this purpose, effort was made to select the most recent studies using predefined search criteria that included at least one of the following keywords in the PubMed and Medline databases: glioblastoma, drug delivery, blood–brain barrier, nanotechnology, and nanoparticle.Conclusion:Breakthrough in nanotechnology offers promising applications in cancer therapy and targeted drug delivery. However, more efforts need to be devoted to the development of novel therapeutic strategies that enable the delivery of drugs to desired areas of the brain with limited side-effects and higher therapeutic efficiency. [ABSTRACT FROM AUTHOR]

Context: Paclitaxel (PTX) and carboplatin (CBP) are widely used for the combined chemotherapy of non-small cell lung cancer (NSCLC). However, the development of multidrug resistance of cancer cells, as well as systemic toxic side effects resulting from nonspecific localization of anticancer drugs to non-tumor areas are major obstacles to the success of chemotherapy in treating cancers. Objective: This study aimed to engineer a prodrug-based nano-drug delivery system for co-encapsulate hydrophilic (CBP) and hydrophobic anti-tumor drugs (PTX). This system was expected to resolve the multidrug resistance cause by single drug, and the dual-drug-loaded liposome was also planned to specifically target the cancer cells without obvious influence on normal cells and tissues. Methods: In this paper, PLGA-PEG-CBP was synthesized by the conjugation between the carboxylic group of PLGA-PEG-COOH and the amino group of CBP. Then, self-assembled nanoparticles for combination delivery of PTX and PLGA-PEG-CBP (PTX/CBP NPs) were prepared by solvent displacement technique. Thein vitroandin vivoanti-tumor efficacy was assessed in NCL-H460 human non-small cell lung carcinoma cell line. Results: PTX/CBP NPs achieved the highest cytotoxic effect among all formulationsin vitro, as compared with single drug delivery NPs.In vivoinvestigation on NSCLC animal models showed that co-delivery of PTX and CBP possessed high tumor-targeting capacity and strong anti-tumor activity. Conclusions: The PTX/CBP NPs constructed in this research offers an effective strategy for targeted combinational lung cancer therapy. [ABSTRACT FROM AUTHOR]

BackgroundThis paper reports a study of 21 patients with peritoneal carcinomatosis from ovarian cancer who underwent cytoreductive surgery and HIPEC by means of PRS-1.0 Combat®, a new model for closed abdomen HIPEC aimed at improving fluid distribution with assistance from a CO2recirculation system. This new technology has been previously shown to be successful in an experimental study (pig model) performed by our group, and has been approved for use in our hospital.MethodsTwenty-one patients with peritoneal carcinomatosis of ovarian cancer origin were included in the study. Cytoreductive surgery and HIPEC were performed by a closed abdomen fluid and CO2recirculation technique using the PRS-1.0 Combat®model. We analysed the intraoperative safety tolerance and post-operative morbidity and mortality during the first 30 days.ResultsBetween November 2011 and March 2014 21 patients with epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stage II–IV, were included in the study. During the procedure there were no significant haemodynamic or analytical disturbances. Complication rates were 38.1% and 57.14% for grade III/IV and minor (grade I/II) complications, respectively. Post-operative mortality was 4.76% (one patient). Complete cytoreductive surgery and intraperitoneal chemotherapy improved overall survival and disease-free survival in women with advanced ovarian cancer. The association of intra-abdominal hyperthermia with chemotherapy (HIPEC) increased the therapeutic benefit.ConclusionsThis study has shown that closed abdomen intraperitoneal chemohyperthermia by a fluid and CO2recirculation system (PRS-1.0 Combat®) can be a safe and feasible model for the treatment of peritoneal carcinomatosis of ovarian cancer origin. [ABSTRACT FROM PUBLISHER]

In this paper, we propose a method to optimise a theoretical control on a mathematical model of interactions between cancer cells and the immune system. The model consists of five ordinary differential equations describing the behaviour of a tumour cell population interacting with populations of immune cells, all cells being submitted to the effects of chemotherapy. Two constraints were added to reflect the biological specificity of the problem. The first one asserts that the number of cytotoxic T lymphocytes must remain above a given threshold at the terminal point in time. The second one keeps the drug concentration in the bloodstream below a threshold to reduce toxic side effects resulting from the damages of chemotherapy to healthy cells. Using Pontryagin’s Maximum Principle and approximation methods for optimal control, we obtain bang–bang solutions for different scenarios. [ABSTRACT FROM PUBLISHER]

BackgroundExtrapulmonary small cell carcinoma (SmCC), also known as oat cell carcinoma or small cell neuroendocrine carcinoma, is characterized by an aggressive clinical course with early metastasis pattern and a short life expectancy. So far, there is no prospective, data-based case–control study due to its low incidence. The purpose of this paper is to discuss the epidemiology, morphopathology, clinical characteristics, differential diagnosis and treatment of bladder SmCC in the light of the literature. ScopePubMed and American Society of Clinical Oncology Meeting abstracts were searched according to the following keywords: ‘extrapulmonary SmCC’, ‘bladder cancer’, and ‘therapeutic approach’. The last search was performed on 1 October 2015. Some additional papers were determined by reviewing references of the appropriate articles. Most of the data regarding small cell carcinoma of the urinary bladder (SmCCB) were found to be based on the retrospective trials. FindingsBladder SmCC is more frequent in men and usually appears in the seventh to eighth decades. Macroscopic hematuria is the most common clinical symptom. The diagnosis of SmCCB is performed based on the same criteria determined by the WHO classification for the diagnosis of small cell lung carcinoma (SCLC). Prognosis is closely correlated with the stage at presentation. Although the prognosis of the disease is poor, a long survival can be achieved particularly by radical surgery following neoadjuvant chemotherapy in patients with early stage tumors. Cystectomy is still the current standard local treatment. However, cystectomy alone is not sufficient. Chemotherapy and definitive radiotherapy should be preferred for limited disease in patients who are not candidate for surgery. ConclusionConsidering the poor prognosis of the disease, further studies are needed to determine the optimal treatment options and new molecular markers in the way of early diagnosis and favorable outcomes. Prospective, multicenter, randomized studies are required to evaluate the role of neoadjuvant chemotherapy followed either by surgery or radiotherapy. [ABSTRACT FROM PUBLISHER]

10-Hydroxycamptothecin (HCPT) is a clinical therapy agent against hepatoma. The chemotherapy of HCPT is strongly obstructed by the emergence of multidrug resistance (MDR), serious systemic toxicity, malfunction of rapid phagocytic and renal clearance disorder which are undesirable for its chemotherapy. In this paper, a drug delivery system (DDS) for HCPT has been developed in order to overcome MDR. Nanostructured lipid carriers (NLC) coated with xyloglucan (XG) was prepared by soya oil and XG consisting of side chains with galactose residues, a terminal moiety that can be used to target HCPT to hepatoma. The therapeutic potential of XG-NLC/HCPT was investigated on HepG2/HCPT cells and on human tumor xenograft nude mouse model (implanted with HepG2/HCPT cells). XG-NLC/HCPT not only indicated superior cytotoxicity against the drug resistant HepG2 cells but alsoin vivo, generated a higher therapeutic effect. Systemic toxicity study demonstrated that the carrier reduced systemic toxicity. XG-NLC/HCPT proved a great potential to serve as DDS to overcome MDR of HepG2/HCPT cells. These results suggested that XG NLC/HCPT represent a promising carrier for drug delivery to the hepatoma and reverse the drug resistant of HepG2 cells and XG could be exploited as a potential targeting device for liver tissue. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the leading cause of death from gynecologic malignancy in the United States. While the treatment options have improved with conventional cytotoxic chemotherapy and advanced surgical techniques, disease recurrence is common and fatal in nearly all cases. Current evidence suggests that the immune system and its ability to recognize and eliminate microscopic disease is paramount in preventing recurrence. The goal of immunotherapy is to balance the activation of the immune system against cancer while preventing the potential for tremendous toxicity elicited by immune modulation. In this paper we will review the role of immune system in disease pathogenesis and different immunotherapies available for the treatment of ovarian cancer as well as current ongoing studies and potential future directions. [ABSTRACT FROM PUBLISHER]

Purpose: Hyperthermia is a cancer treatment technique that could be delivered as a stand-alone modality or in conjunction with chemotherapy or radiation therapy. Noninvasive and real-time temperature monitoring of the heated tissue improves the efficacy and safety of the treatment. A temperature-sensitive acoustic parameter is required for ultrasound-based thermometry. In this paper the amplitude and the energy of the acoustic harmonics of the ultrasound backscattered signal are proposed as suitable parameters for noninvasive ultrasound thermometry. Materials and methods: A commercial high frequency ultrasound imaging system was used to generate and detect acoustic harmonics in tissue-mimicking gel phantoms and ex vivo bovine muscle tissues. The pressure amplitude and the energy content of the backscattered fundamental frequency (p1 and E1), the second (p2 and E2) and the third (p3 and E3) harmonics were detected in pulse-echo mode. Temperature was increased from 26° to 46 °C uniformly through both samples. The amplitude and the energy content of the harmonics and their ratio were measured and analysed as a function of temperature. Results: The average p1, p2 and p3 increased by 69%, 100% and 283%, respectively as the temperature was elevated from 26° to 46 °C in tissue samples. In the same experiment the average E1, E2 and E3 increased by 163%, 281% and 2257%, respectively. A similar trend was observed in tissue-mimicking gel phantoms. Conclusions: The findings suggest that the harmonics generated due to nonlinear ultrasound beam propagation are highly sensitive to temperature and could potentially be used for noninvasive ultrasound tissue thermometry. [ABSTRACT FROM AUTHOR]

Purpose: Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry.Materials and methods: The records of 175,538 clinical trials registered at ClinicalTrials.gov were downloaded on 29 September 2014 and a database was established. We searched this database for hyperthermia or equivalent words.Results: A total of 109 trials were identified in which hyperthermia was part of the treatment regimen. Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion. Seven trials (6%) were testing perfusion attempts to other locations (thoracic/pleuraln = 4, limbn = 2, hepaticn = 1). Sixteen trials (15%) were testing regional hyperthermia, 13 trials (12%) whole body hyperthermia, seven trials (6%) superficial hyperthermia and two trials (2%) interstitial hyperthermia. One remaining trial tested laser hyperthermia.Conclusions: In contrast to the general opinion, this analysis shows continuous interest and ongoing clinical research in the field of hyperthermia. Interestingly, the majority of trials focused on some form of intraperitoneal hyperthermic chemoperfusion. Despite the high number of active clinical studies, HIPEC is a topic with limited attention at the annual meetings of the European Society for Hyperthermic Oncology and the Society of Thermal Medicine. The registration of on-going clinical trials is of paramount importance for the achievement of a comprehensive overview of available clinical research activities involving hyperthermia. [ABSTRACT FROM PUBLISHER]

Objectives The aim of this paper is to review the pathogenesis and diagnostic approaches to anemia in cancer patients. Methods PubMed was queried for various combinations of anemia and cancer-related terms using appropriate filters for articles and practice guidelines published in the last 5 years. Specific searches were conducted for individual pathogenetic mechanisms and malignancies of specific anatomic sites. Results Anemia is the commonest hematological manifestation of cancer, afflicting 40–64% of patients treated for malignancies. Pathophysiologically, cancer-related anemia can be classified into four broad but overlapping categories: hypoproliferative anemia including the common anemia of inflammation/chronic disease, hemolytic anemia, miscellaneous etiologies, and uncertain etiologies. Anemia incidence increases with the administration of chemotherapy/radiotherapy. It reduces the quality of life and shortens survival in cancer patients. A positive correlation is observed between anemia and tumor hypoxia. Experimentally, hypoxemia enhances tumor growth and resistance to therapy by stimulating angiogenesis, acquisition of genomic mutations, and increasing resistance to apoptosis as well as to the killing effects of chemo/radiotherapy-generated free radicals. Discussion Diagnostic approaches to the anemic cancer patient begin with a detailed clinical history and physical examination. Peripheral blood morphology and reticulocyte count are also helpful. Patients with unexplained anemia are evaluated by standard approaches also used in patients of similar age without malignancy. Serum iron profile and bone marrow examination are often required in difficult cases. This review focuses on major aspects of the pathogenesis of the individual entities. Diagnostic approaches and uncommon causes including hemophagocytic lymphohistiocytosis, acquired hemoglobinopathies, and myelodysplasia are also discussed. [ABSTRACT FROM AUTHOR]

Retinoblastoma has the unique capacity to accelerate its own intra-ocular propagation by adopting semi-solid or even liquid growth properties through seeding. Until recently, the presence of any degree of seeding was mostly incompatible with successful conservative management, due to the multiresistant nature of the seeds. Surprisingly, this well-recognized retinoblastoma behavior has not undergone any detailed description of seeding patterns and anatomic sites. In this paper, we describe the phenotypic variability of seeds across the four possible intraocular seeding compartments and classify them into three fundamental types: namely dust, spheres, and clouds. We also provide an overview of the different therapeutic strategies developed for seeding, with special attention to intravitreal chemotherapy as the treatment of choice for vitreous and retro-hyaloid seeding. Finally, we propose criteria to enable assessment of the response to treatment by reporting seed regression patterns, as well as a clinical grading system for the retinal toxicity observed following intravitreal melphalan. [ABSTRACT FROM AUTHOR]

To compare the efficacy and side effects of salvage chemotherapy between etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) and ifosfamide, carboplatin and etoposide plus dexamethasone (DICE) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Medical records of patients with relapsed or refractory DLBCL receiving second-line ESHAP or DICE chemotherapy with or without rituximab from January 2007 to November 2022 were retrospectively reviewed. The primary objective was progression-free survival (PFS). The secondary objectives were overall survival (OS), overall response rate (ORR) and adverse events (AEs). Seventy patients were enrolled including 21 patients who received ESHAP and 49 patients who received the DICE regimen. Six patients (28.6%) and 19 patients (38.8%) in the ESHAP and DICE groups underwent ASCT, respectively. The ORR was 47.6% for ESHAP and 53.1% for DICE (p =.67). The two-year PFS was 14.3% for ESHAP and 26.5% for DICE (p =.33) with median PFS of 5 months and 14 months, respectively (hazard ratio 0.74; 95% CI 0.39–1.36, p =.330). The two-year OS was 14.3% for ESHAP and 26.5% for DICE (p =.37) with median OS of 8 months and 19 months, respectively. Patients in ESHAP group have more all-grade renal impairment than DICE group (23.8% vs. 6.1%, p =.047). Efficacy between ESHAP and DICE regimens as salvage chemotherapy for relapsed or refractory DLBCL was not significantly different in terms of two-year PFS, two-year OS and ORR. DICE regimen had less renal AE than ESHAP. [ABSTRACT FROM AUTHOR]

Vincamine, a natural chemical, was used as a reducing agent in the synthesis of IgG antibodies mediated biogenic gold nanoparticles (IgGAuNPs). Eventually, the synthesised IgGAuNPs were bioconjugated with the chemotherapeutic drug methotrexate (MTX-IgGAuNPs). The IgG isotype can target cancer cells through polymorphic Fc gamma receptors (FccRs) and have therapeutic effects. They can restrict cell division by inhibiting different intracellular signal transduction pathways and activating NK cells and macrophages through antibody-dependent cellular cytotoxicity and macrophage-mediated antibodydependent phagocytosis, respectively. Further, IgGAuNPs and MTX-IgGAuNPs were characterised by physical techniques. Moreover, 3D conformational changes in the structure of IgG were analysed by fluorescence spectroscopy during and after the synthesis of IgGAuNPs. Furthermore, the IgGAuNPs and MTX-IgGAuNPs were effective against lung cancer (A549 cells), while they were found to be non-toxic against normal cells (NRK cells). The effectiveness of IgGAuNPs and MTX-IgGAuNPs was examined by MTT cytotoxicity assay, DCFDA method for the production of ROS, and release of Cyt-c from the mitochondria for caspase-3-mediated apoptosis. Moreover, the confirmation of internalisation of particles into the nucleus was examined under the DAPI assay, and it was found that particles caused nuclear fragmentation, which was also an indication of apoptosis. [ABSTRACT FROM AUTHOR]

Over the past 50 years, 5-fluorouracil (5-FU) has played a critical role in the systemic chemotherapy of cancer patients. Bolus intravenous (IV) 5-FU infusion has been used due to the limitation of its extremely short half-life (10–15 min). This study used ultrasound (US) mediating 5-FU-loaded microbubbles (MBs) cavitation as a tool to increase local intratumoral 5-FU levels with a reduced dose of 5-FU (a single IV injection of 2.5 mg/kg instead of a single intraperitoneal injection of 25–200 mg/kg as used in previous studies in mice). The 5-FU-MBs were prepared with a 132 mg/mL albumin solution and a 0.30 mg/mL 5-FU solution. The diameters of the MBs and 5-FU-MBs were 1.24 ± 0.85 and 2.00 ± 0.53 µm (mean ± SEM), respectively, and the maximum loading efficiency of 5-FU on MBs was 19.04 ± 0.25%. In the in vitro study, the cell viabilities of 5-FU and 5-FU-MBs did not differ significantly, but compared with the 5-FU-MBs treatment-alone group, cell toxicity increased to 31% in the 5-FU-MBs + US group (p < 0.001). The biodistribution results indicated that the 5-FU levels of the tumors in small animals were significant higher for the 5-FU-MBs + US treatment than for either the 5-FU-MBs or 5-FU treatment with low 5-FU systemic treatment doses (2.5 mg/kg 5-FU IV). In small-animal treatment, 2.5 mg/kg 5-FU therapeutic IV doses injected into mice caused a more-significant reduction in tumor growth in the 5-FU-MBs + US group (65.9%) than in the control group after 34 days of treatment. [ABSTRACT FROM AUTHOR]

Ocular surface squamous neoplasia (OSSN) is a broad pathological entity that includes squamous neoplasm of conjunctival and corneal tissue. These various malignancies include conjunctival intraepithelial neoplasia (CIN), corneal epithelial dysplasia, squamous cell carcinoma (SCC), and mucoepidermoid carcinoma. OSSN diagnosis rests on exfoliative cytology, vital dyes, and imaging in the form of confocal microscopy and anterior segment optical coherence tomography. The medical management modalities are topical chemotherapy (Mitomycin C and 5 fluorouracil), immunotherapy (Interferon alpha 2b), and upcoming drugs, such as antivirals, anti-VEGF, and retinoic acid. Excision biopsy with no touch technique remains the gold standard for managing OSSN. However, surgery can lead to recurrence and unfavorable results in some cases. This article provides insights into the treatment aspects of OSSN with an overview of recent updates. The authors have discussed the current concept regarding the medical and surgical management of OSSN. The authors also dwell upon the recent updates along with the expert opinion. Although surgery remains the gold standard, topical drugs have revolutionized the management of OSSN. Patients should be closely followed up to look for any side effects. Cost, time duration, cosmesis, and side are the remaining major factors in deciding for medical versus surgical therapy. [ABSTRACT FROM AUTHOR]

Purpose: Ths paper reports a pilot/feasibility trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) prior to transurethral resection of bladder tumour (TURBT) for non-muscle invasive bladder cancer (NMIBC). Materials and methods: A pilot/feasibility clinical trial was performed and 15 patients with intermediate to high-risk NMIBC received HIVEC prior to TURBT. HIVEC consisting of eight weekly instillations of intravesical MMC (80 mg in 50 mL) delivered with the novel Combat BRS® system at a temperature of 43 °C for 60 min. Treatment-related adverse effects were measured and patients were followed for 2 years for disease recurrence. Results: A total of 119 HIVEC treatments occurred. Grade 1 adverse events consisted of irritative bladder symptoms (33%), bladder spasms (27%), pain (27%), haematuria (20%) and urinary tract infection (UTI; 14%). Grade 2 adverse events were bladder calcification (7%) and reduced bladder capacity (7%). No grade 3 or higher toxicity was observed. At TURBT, eight patients (53%) were complete responders (pT0) while seven (47%) were partial responders. With a median follow-up of 29 months, the 3-year cumulative incidence of recurrence was 15%. Conclusions: The Combat BRS® system achieved target bladder temperatures and delivered HIVEC with a favourable side-effect profile. Our pilot trial also provides preliminary evidence of treatment efficacy. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this paper is to report thermal dosimetry characteristics of external deep regional pelvic hyperthermia combined with intravesical mitomycin C (MMC) for treating bladder cancer following transurethral resection of bladder tumour, and to use thermal data to evaluate reliability of delivering the prescribed hyperthermia dose to bladder tissue. Materials and methods: A total of 14 patients were treated with MMC and deep regional hyperthermia (BSD-2000, Sigma Ellipse or Sigma 60). The hyperthermia objective was 42° ± 2 °C to bladder tissue for ≥40 min per treatment. Temperatures were monitored with thermistor probes and recorded values were used to calculate thermal dose and evaluate treatment. Anatomical characteristics were examined for possible correlations with heating. Results: Combined with BSD-2000 standard treatment planning and patient feedback, real-time temperature monitoring allowed thermal steering of heat sufficient to attain the prescribed thermal dose to bladder tissue within patient tolerance in 91.6% of treatments. Mean treatment time for bladder tissue >40 °C was 61.9 ± 11.4 min and mean thermal dose was 21.3 ± 16.5 CEM43. Average thermal doses obtained in normal tissues were 1.6 ± 1.2 CEM43 for the rectum and 0.8 ± 1.3 CEM43 in superficial normal tissues. No significant correlation was seen between patient anatomical characteristics and thermal dose achieved in bladder tissue. Conclusions: This study demonstrates that a hyperthermia prescription of 42° ± 2 °C for 40-60 min can be delivered safely to bladder tissue with external radiofrequency phased array applicators for a typical range of patient sizes. Using the available thermometry and treatment planning, the BSD-2000 hyperthermia system was shown to be an effective method of focusing heat regionally around the bladder with good patient tolerance. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to evaluate the safety and heating efficiency of external deep pelvic hyperthermia combined with intravesical mitomycin C (MMC) as a novel therapy for non-muscle-invasive bladder cancer (NMIBC). Materials and methods: We enrolled subjects with bacillus Calmette-Guérin (BCG) refractory NMIBC to an early phase clinical trial of external deep pelvic hyperthermia (using a BSD-2000 device) combined with MMC. Bladders were heated to 42 °C for 1 h during intravesical MMC treatment. Treatments were given weekly for 6 weeks, then monthly for 4 months. Heating parameters, treatment toxicity, and clinical outcomes were systematically measured. Results: Fifteen patients were enrolled on the clinical trial. Median age was 66 years and 87% were male. Median European Organisation for Research and Treatment of Cancer (EORTC) recurrence and progression scores were 6 and 8, respectively. The full treatment course was attained in 73% of subjects. Effective bladder heating was possible in all but one patient who could not tolerate the supine position due to lung disease. Adverse events were all minor (grade 2 or less) and no systemic toxicity was observed. The most common adverse effects were Foley catheter pain (40%), abdominal discomfort (33%), chemical cystitis symptoms (27%), and abdominal skin swelling (27%). With a median follow-up of 3.18 years, 67% experienced another bladder cancer recurrence (none were muscle invasive) and 13% experienced an upper tract recurrence. Conclusions: External deep pelvic hyperthermia using the BSD-2000 device is a safe and reproducible method of heating the bladder in patients undergoing intravesical MMC. The efficacy of this treatment modality should be explored further in clinical trials. [ABSTRACT FROM AUTHOR]

Clinical trials have shown that hyperthermia (HT), i.e. an increase of tissue temperature to 39-44 °C, significantly enhance radiotherapy and chemotherapy effectiveness [1]. Driven by the developments in computational techniques and computing power, personalised hyperthermia treatment planning (HTP) has matured and has become a powerful tool for optimising treatment quality. Electromagnetic, ultrasound, and thermal simulations using realistic clinical set-ups are now being performed to achieve patient-specific treatment optimisation. In addition, extensive studies aimed to properly implement novel HT tools and techniques, and to assess the quality of HT, are becoming more common. In this paper, we review the simulation tools and techniques developed for clinical hyperthermia, and evaluate their current status on the path from 'model' to 'clinic'. In addition, we illustrate the major techniques employed for validation and optimisation. HTP has become an essential tool for improvement, control, and assessment of HT treatment quality. As such, it plays a pivotal role in the quest to establish HT as an efficacious addition to multi-modality treatment of cancer. [ABSTRACT FROM AUTHOR]

Background: Adjuvant intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) is a therapy which combines thermotherapy and intraperitoneal chemotherapy. It is theoretically powerful for patients with advanced gastric cancer (AGC), but is there evident advantage in clinical practice? We need evidence to guide our decision-making. Objectives: Meta-analysis was performed to assess the effectiveness and safety of adjuvant intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) for patients with resectable locally advanced gastric cancer, and to provide the reference for clinical practice and study. Methods: We searched the Cochrane Library, PubMed, Embase, Web of Science and Chinese databases (Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang) electronically and also retrieved papers from other sources (tracing related references and communication with other authors). All relevant randomised controlled trials (RCTs) were collected to compare surgery combined with IHIC to surgery without IHIC for AGC. There were no language restrictions. After independent quality assessment and data extraction by two reviewers, meta-analysis was conducted by RevMan 5.1 software. Results: 16 RCTs involving 1,906 patients were included. Compared with surgery alone, combination therapy (surgery plus IHIC) was associated with a significant improvement in survival rate at 1 year (hazard ratio (HR) = 2.99; 95% confidence interval (CI) = 2.21 to 4.05; p < 0.00001), 2 years (HR = 2.43; 95%CI = 1.81 to 3.26; p < 0.00001), 3 years (HR = 2.63; 95%CI = 2.17 to 3.20; p < 0.00001), 5 years (HR = 2.49; 95%CI = 1.97 to 3.14; p < 0.00001), and 9 years (HR = 2.14; 95%CI = 1.38 to 3.32; p = 0.0007). Compared with surgery alone, combination therapy was associated with a significant reduction in recurrence rate at 2 years (RR = 0.42; 95%CI = 0.29 to 0.61; p < 0.00001), 3 years (RR = 0.35; 95%CI = 0.24 to 0.51; p < 0.00001) and 5 years (RR = 0.47; 95%CI = 0.39 to 0.56; p < 0.00001). IHIC was not found to be associated with higher risks of anastomotic leakage, ileus, bowel perforation, myelosuppression, gastrointestinal reaction and hypohepatia, but it increased the incidence of abdominal pain (RR = 21.46; 95%CI = 5.24 to 87.78; p < 0.00001). Conclusions: Compared with surgery alone, surgery combined with IHIC can improve survival rate and reduce the recurrence rate, with acceptable safety. However, safety outcomes should be further evaluated by larger samples and high quality studies. Additionally, hyperthermia for the intraperitoneal chemotherapy needs more clinical research. [ABSTRACT FROM AUTHOR]

Chemotherapy in treatment of malignant tumors has many side effects due to the poor physiochemical properties and the toxicity to normal tissues. The dual-targeting drug delivery system combining two high-affinity ligands can target anticancer drug primary to the diseased tissue, then to the tumor, which provides both greater efficacy of treatment and less harm to normal tissues. In this paper, a novel dual-targeting moiety RGD7 (R-G-D-D-D-D-D-D-D; Nonapeptide for bone cancer combining D6 peptide as bone target moiety and RGD peptide as tumors target moiety was contracted. A series of bone and/or tumor targeting conjugates have been synthesized in a convergent approach and well characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. The hydroxyapatite (HAP) binding, water solubility, the drug release and the distribution in vivo were evaluated. All the conjugates were water-soluble and able to release the parent drugs in vitro. The bone-targeting property of the dual-targeting delivery system was enhanced from the results of the HAP binding and the distribution in vivo. The experiment for verifying tumor targeting property was underway. These results provided an effective entry to the development of a new dual-targeting delivery system for bone cancer. [ABSTRACT FROM AUTHOR]