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Context: Shenqi FuZheng injection (SFI) has been suggested as a complementary treatment of chemotherapy in China. However, little is known about it in western countries. Objective: This study assesses the clinical effect of SFI combined with chemotherapy for breast cancer patients. Materials and methods: Both English and Chinese databases were searched covering the time period of 1999– 2018 for relevant studies comparing the effect of SFI plus chemotherapy treatment with chemotherapy alone in patients with breast cancer. Target outcomes concerning treatment effect, performance status, immune system and toxic effects were extracted and combined using Stata version 15.0 software. Quality assessment was performed using the Jadad scale. Results: Forty-nine trials were included based on certain selection criteria. Only seven studies were rated as high-quality publications. Results of meta-analysis showed that SFI intervention can significantly improve objective tumour response, performance status, NK, CD3+, CD4+ and CD4+/CD8+ ratio and reduce occurrence of leucopenia, thrombocytopenia, haemoglobin reduction, liver dysfunction, gastrointestinal reaction, nausea and vomiting, bone marrow suppression and ECG changes. However, no significant difference was found between SFI and the control group regarding CD8+ levels, and renal disorders. Discussion and conclusions: SFI intervention appeared to be effective in improving clinical efficacy, immune function and reducing toxicity when combined with chemotherapy for breast cancer. However, our findings still need verification by high-quality trials. [ABSTRACT FROM AUTHOR]

Drug combination represents one of the most accredited strategies of cancer therapy able to improve drug efficacy and possibly overcome drug resistance. Among the agents used to complement conventional chemotherapy, carbonic anhydrase IX (CAIX) inhibitors appear as one of the most suitable, as markers of hypoxic and acidic cancer cells which do not respond to chemo- and radiotherapy. We performed preclinical in vitro assays to evaluate whether the SLC-0111 CAIX inhibitor co-operates and potentiates the cytotoxic effects of conventional chemotherapeutic drugs in A375-M6 melanoma cells, MCF7 breast cancer cells, and HCT116 colorectal cancer cells. Here, we demonstrate that the SLC-0111 CAIX inhibitor potentiates cytotoxicity of Dacarbazine and Temozolomide currently used for advanced melanoma treatment. SLC-0111 also increases breast cancer cell response to Doxorubicin and enhances 5-Fluorouracil cytostatic activity on colon cancer cells. These findings disclose the possibility to extend the use of CAIX inhibitors in the combination therapy of various cancer histotypes. [ABSTRACT FROM AUTHOR]

Although intraperitoneal chemotherapy (IPC) has evolved into an established treatment modality for patients with peritoneal metastasis (PM), drug penetration into tumor nodules remains limited. Drug transport during IPC is a complex process that depends on a large number of different parameters (e.g. drug, dose, tumor size, tumor pressure, tumor vascularization). Mathematical modeling allows for a better understanding of the processes that underlie drug transport and the relative importance of the parameters influencing it. In this work, we expanded our previously developed 3D Computational Fluid Dynamics (CFD) model of the drug mass transport in idealized tumor nodules during IP chemotherapy to include realistic tumor geometries and spatially varying vascular properties. DCE-MRI imaging made it possible to distinguish between tumorous tissues, healthy surrounding tissues and necrotic zones based on differences in the vascular properties. We found that the resulting interstitial pressure profiles within tumors were highly dependent on the irregular geometries and different zones. The tumor-specific cisplatin penetration depths ranged from 0.32 mm to 0.50 mm. In this work, we found that the positive relationship between tumor size and IFP does not longer hold in the presence of zones with different vascular properties, while we did observe a positive relationship between the percentage of viable tumor tissue and the maximal IFP. Our findings highlight the importance of incorporating both the irregular tumor geometries and different vascular zones in CFD models of IPC. [ABSTRACT FROM AUTHOR]

Cisplatin is the most commonly used antitumor drug in the chemotherapy of a variety of malignancies. However, the severe side effects and drug resistance limit its clinical application. The aim of this study was to develop PLGA-based cisplatin-loaded implants and evaluate the antitumor efficacy of continuous intratumoral chemotherapy with the implants. The cisplatin-loaded implants were prepared by the direct compression method and characterized regarding drug content, micromorphology, in vitro and in vivo drug release profiles. Furthermore, the antitumor activity of the implants was conducted in sarcoma 180 tumor-bearing mice. The SEM images showed smooth surface of the implants and the mean drug content of the tested implants was (37.7% ± 0.5%, w/w). Both in vitro and in vivo release profiles of the implants were characterized by initial burst release followed by the sustained-release of cisplatin. Intratumoral implantation of the cisplatin-loaded implants could effectively inhibit the tumor growth. Additionally, intratumoral chemotherapy with the implants significantly reduced the systemic toxicity compared with intravenous injection of cisplatin. It is worth noting that an increase in the dose of the implants led to a higher tumor suppression rate without additional systemic toxicity. These results demonstrated that cisplatin-loaded implants enhanced the antitumor efficacy and reduced the dose-related side effects in sarcoma 180 tumor-bearing mice. [ABSTRACT FROM AUTHOR]

Background: This research is to evaluate patients with retinoblastoma, who receive chemotherapy, with enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) to compare the signs of retinopathy. Materials and Methods: A prospective non-randomized trial included 125 eyes of 74 patients at the age of 24 ± 1.6 months with retinoblastoma. All patients underwent an ophthalmoscopic examination and EDI-OCT before therapeutic treatment. The test group consisted of 55 patients, who underwent a course of chemotherapy. Patients were divided into two groups depending on the type of chemotherapy. Group #1 patients received six cycles of systemic intravenous chemotherapy treatment, ophthalmoscopic examination, and EDI-OCT occurred after third cycle and sixth cycle. Group #2 underwent three cycles of IVC chemotherapy treatment, and then local chemotherapy – three cycles of super-selective intra-arterial chemotherapy for exophytic retinoblastoma and 9 procedures of intravitreal (IVT) for endophytic retinoblastoma. Eyes in the control group were affected by eccentric neoplasms but macula and the optic nerve were not damaged. Results: After six cycles of IVC chemotherapy treatment, Group #1 history expanded with atrophy-induced peripapillary nerve fiber layer thinning (33.9%). At three cycle of super-selective intra-arterial chemotherapy, OCT imaging in Group #2 revealed more related symptoms like retinal vascular distention in peritumoral area. After systemic and intravitreal chemotherapy, macular puckers and small hyperreflective dotted foci in the inner retina were tracked. In Group #3 affected by peripheral tumors, the topographic anatomy of the macula was normal prior to therapy. Conclusion: Profound morphometric disturbances that come with combined chemotherapy call for a more careful treatment with methods selected in terms of OCT findings and specific chemotherapy contraindications. [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy of pembrolizumab relative to other treatments used in stage III melanoma by conducting a systematic literature review (SLR) and network meta-analysis (NMA). Methods: A SLR was conducted to identify randomized clinical trials (RCTs) evaluating approved adjuvant treatments including interferon-containing regimens, BRAF-inhibitors, and PD-L1 inhibitors in stage III melanoma patients. Relative treatment effects for recurrence-free survival (RFS) were synthesized with Bayesian NMA models that allowed for hazard ratios (HRs) to vary over time. Results: Included studies formed a connected network of evidence composed of eight trials. In high-risk stage III patients, the HR for pembrolizumab vs observation decreased significantly over time with the superiority of pembrolizumab over observation becoming statistically meaningful before 3 months. By 9 months, the HR for pembrolizumab vs observation was statistically significantly lower than the HR for most other treatments vs observation, with the exception of ipilimumab and biochemotherapy due to overlapping 95% credible intervals. In BRAF + patients, pembrolizumab was statistically significantly better than observation after 3 months. The HR for both BRAF-inhibitors vs observation increased significantly over time and pembrolizumab was statistically superior to both BRAF-inhibitors after 15 months. Conclusions: Pembrolizumab results in statistically significantly improved RFS compared to all competing regimens after 9 months, except ipilimumab and biochemotherapy, for the adjuvant treatment of stage III melanoma. However, point estimate HRs vs observation for pembrolizumab are much lower than those for ipilimumab. In BRAF + patients, the advantage of pembrolizumab versus competing interventions increases over time with respect to RFS. [ABSTRACT FROM AUTHOR]

Objective: The aim of this survey conducted by 20 leading Spanish oncologists was to analyze the concurrence between Spanish clinical practice and the recently published definition of the optimal sequence for the systemic treatment of metastatic breast cancer (MBC) according to patient profiles. Methods: A self-administered questionnaire was developed, divided into five sections comprising 34 specific questions related to sequential treatments, plus three additional general questions. Respondents were asked to justify negative answers. Participants were recruited randomly by invitation out of a total of 619 oncologists. The questionnaire was sent and collected via e-mail between October 2015 and May 2016. A total of 191 completed questionnaires were received. Results: Overall, 70% of oncologists would keep the three patient profiles exactly as proposed (hormone receptor-positive and HER2-negative, HER2-positive, and triple negative breast cancer). Affirmative answers to questions regarding treatment sequences for these patient profiles (1–34) ranged from 77.8–99.5%, with an average of 90.9% of oncologists being in agreement with the recommended sequential treatments. The lowest degree of consensus was observed for endocrine treatments in pre-menopausal women and for chemotherapy options in hormone-resistant patients, whilst the highest degree of consensus was reached for targeted therapies in HER2-positive patients and for endocrine therapy in post-menopausal women. In their comments, participants revealed a number of economic constraints that prevented them from implementing some of the best treatment options. Conclusions: In conclusion, despite the complexity of MBC treatment, there is general agreement on the optimal treatment sequences. [ABSTRACT FROM AUTHOR]

Paraneoplastic syndrome is a rare but reversible cause of non-thyroid-related extraocular muscle enlargement. We present a 71-year-old lady with diplopia, restricted eye movements, suppressed thyroid-stimulating hormone and enlargement of all extraocular muscles while on thyroxine replacement for hypothyroidism. She had distant history of metastatic breast cancer treated with chemotherapy, surgical resection and tamoxifen. She had negative anti-thyroid autoantibodies and thyroid ultrasound was not consistent with autoimmune thyroid disease. Carcinoembryonic antigen and cancer antigens 15-3, 125 and 72-4 were elevated, and whole-body positron emission tomography-computed tomography showed avid liver, left adrenal and skeletal lesions, with liver biopsy confirming breast cancer recurrence. She received prednisone and chemotherapy (letrozole, palbociclib) and achieved normalisation of eye movements and reduction in her EOME at 9-month follow-up. Our case highlights the importance of exploring paraneoplastic syndrome as a treatable cause of EOME in a patient lacking features of thyroid orbitopathy and autoimmune thyroid disease. [ABSTRACT FROM AUTHOR]

Objective: To identify any change in quality of life (QoL) caused by chemotherapy-induced toxicities, such as hearing loss and tinnitus, to provide information in order to improve services and aid clinicians in their decision-making. Design: This systematic review followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist. The search terms were cancer, platinum-based chemotherapy, ototoxicity and "quality of life". Titles and abstracts, followed by full texts, were screened by two independent researchers. The relevant data were extracted and quality analysis was performed using the NIH Quality Assessment Tool. Study sample: About 308 titles and abstracts were screened, and 27 full-text articles were screened. Ten articles representing 11 studies were included in the review. Study design included cross-sectional studies, randomised control trials and longitudinal studies. Results: Diagnostic criteria consisted of audiograms, questionnaires and patient complaints. The study quality ranged from 21.43% to 85.71%. Overall results found that those treated with cisplatin had more hearing loss and tinnitus than those treated with other therapies. Furthermore, those with hearing loss and tinnitus were more likely to have a lower QoL. Conclusions: There is an urgent need to standardise diagnostics when investigating ototoxicity and its effect on QoL, particularly for research into risk factors, prevention and management. [ABSTRACT FROM AUTHOR]

Gelatin nanoparticles (GN) with an intrinsic antimicrobial activity maybe a good choice to improve the effectiveness of photodynamic antimicrobial chemotherapy (PACT). The aim of this study was to development gelatin nanoparticles loaded methylene blue (GN-MB) and investigate the effect of GN-MB in the Candida albicans growth by PACT protocols. The GN and GN-MB were prepared by two-step desolvation. The nanoparticulate systems were studied by scanning electron microscopy and steady-state techniques, the in vitro drug release was investigated, and we studied the effect of PACT on C. albicans growth. Satisfactory yields and encapsulation efficiency of GN-MB were obtained (yield = 76.0% ± 2.1 and EE = 84.0% ± 1.3). All the spectroscopic results presented here showed excellent photophysical parameters of the studied drug. Entrapment of MB in GN significantly prolongs it's in vitro release. The results of PACT experiments clearly demonstrated that the photosensitivity of C. albicans was higher when GN-MB was used. Gelatin nanoparticles loaded methylene blue–mediated photodynamic antimicrobial chemotherapy may be used against Candida albicans growth. [ABSTRACT FROM AUTHOR]

Background: Approximately 50% of survivors of childhood acute lymphoblastic leukemia (ALL) demonstrate cognitive impairments. However, the trajectory of change and contributing neuropathology is unclear, limiting our ability to tailor intervention content and timing. This study aimed to explore information processing abilities and brain morphology early post-treatment for pediatric ALL. Procedure: Twenty-one children at the end of ALL treatment and 18 controls underwent neuropsychological assessment. A subset also completed structural magnetic resonance imaging. Results: A principal component analysis generated two cognitive factors: information processing capacity and information processing speed. Compared to control group, the ALL group displayed deficits in capacity, but not speed. No group differences were identified in morphology. No relationship was identified between capacity or speed and morphology. Conclusion: Early cognitive intervention should target information processing abilities using a system-wide approach. Future studies should employ alternative imaging techniques sensitive to white-matter microstructure when exploring pathology underlying information processing deficits. [ABSTRACT FROM AUTHOR]

Introduction: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour, and its outcome is strongly conditioned by the rapid onset of resistance to conventional chemotherapeutics. First-line treatment with a combination of platinum agents and topoisomerase inhibitors has been the standard of care for over 30 years, with disappointing clinical outcome caused by early-acquired chemoresistance. In this disheartening scenario, novel treatment strategies are being implemented in order to either revert or bypass resistance mechanisms. Areas covered: The general mechanism of action of the standard frontline treatment regimens for SCLC, as well as the known resistance mechanisms to these drugs, is reviewed. Moreover, we focus on the current preclinical and clinical evidence on the potential role of PARP inhibitors and rovalpituzumab tesirine (Rova-T) to tackle chemoresistance in SCLC. Expert opinion: Preliminary evidence supports PARP inhibitors and Rova-T as two promising approaches to either revert or bypass chemoresistance in SCLC, respectively. The identification of potential predictive biomarkers of response to these innovative treatments (SLFN11 and DLL3) has shortened the gap between SCLC and personalized targeted therapy. Further large-scale clinical studies are urgently needed for a better designation of PARP inhibitors and Rova-T in the therapeutic algorithm of SCLC patients. [ABSTRACT FROM AUTHOR]

Introduction: Radiotherapy is a mainstay of solid tumor management but can be associated with unacceptable levels of off-target tissue toxicity which impact treatment outcomes and patients' quality of life. Tumour response to radiotherapy and the frequency and severity of radiotherapy-induced toxicities, especially mucositis, varies among patients. Gut microbiota has been found to modulate both the efficacy and toxicity of some types of cancer chemotherapies and immunotherapies but has yet to be investigated thoroughly in the setting of radiotherapy. Area covered: In this review, we discuss the potential role of gut microbiota on modulating radiotherapy-induced oral and gastrointestinal mucositis and the anti-tumor response to radiotherapy through modulation of immune responses. Expert opinion: The gut microbiota plays a major role in the modulation of systemic immune responses, which influence both radiotherapy response and gastrointestinal toxicities such as mucositis. Hence, investigating the gut microbiota link to the variation in radiotherapy responses and toxicities among patients is warranted. Future targeting of these responses with a patient-tailored restoration of optimal microbial composition could lead to a new era of mucositis prevention and enhanced tumor responses. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-related side effects and their management in patients with Non-Hodgkin's Lymphoma (NHL) are not well defined in developing countries, including Kenya. This needs addressing considering the high number of patients with cancer in these countries. Consequently, we sought to determine the common side effects of chemotherapy used to treat NHL in pediatric patients and its implications.Methods: Observational study conducted at the Kenyatta National Hospital in patients aged ≤15 years. Some data was collected by reviewing patients' records admitted to the pediatric oncology ward, December 2016 to May 2017; and additional data was collected retrospectively (review of patients' records with NHL, January-2014 to May-2017). Data were analyzed descriptively.Results: Overall, out of the identified NHL patients (n = 85), 93% (n = 79) had chemotherapy-related side effects. The majority of patients suffered from side effects were managed; apart from 23% to 24% of the documented anemia and hypersensitivity, respectively.Conclusions: Whilst the majority of the reported side-effects were being managed, the lack of management of some side effects raises real concerns since this indicates either failure to manage or failure to document their management in patients' records, both of which should be addressed appropriately to improve future care. [ABSTRACT FROM AUTHOR]

Purpose: To review the demography and etiology of pediatric enucleation over time. Methods: Pediatric ophthalmic inpatients recruited and recorded (aged 0-14 years) at Shandong Eye Institute from January 2001 to December 2015 were reviewed. Changes during the three periods from 2001 to 2005, 2006 to 2010, and 2011 to 2015 were compared and analyzed. Results: A total of 9307 pediatric inpatients were reviewed. Of these, 71 patients (71 eyes) who had been treated by enucleation were analyzed; 46 were boys (64.79%) and 25 were girls (35.21%). The mean age at enucleation was 9 (0-14) years. The pediatric enucleation rate during this 15-year period was 0.76% (71/9307), with a decreasing trend (p < 0.001). From 2001 to 2005, the figure was 3.45% (43/1245); it dropped to 0.80% (26/3231) from 2006 to 2010 and then dropped further to 0.04% (2/4831) by 2015. Trauma (52.1%, 37/71) was the leading etiology. Overall, 89.2% (33 eyes) exhibited open globe injuries; 78.4% (29/37) of these involved boys. In the cases with open injuries, the mean age at the time of trauma was 6.0 (0-14) years and the mean age at enucleation was 11 (2-14) years. Retinoblastoma (RB) (22.5%, 16/71) was the second-most common etiology; 68.8% (11/16) of these cases involved girls and the mean age at enucleation was 2 (0-5) years. Conclusion: A decrease in pediatric enucleation in North China, especially in Shandong Province, was observed over time, possibly because of better surgical techniques, improvements in the treatment of RB, and public health interventions in children. [ABSTRACT FROM AUTHOR]

Introduction: Platinum-based chemotherapy remains standard-of-care for gastric and gastroesophageal junction (GEJ) adenocarcinoma. For locally advanced resectable disease, perioperative treatment with cisplatin-based doublet or triplet chemotherapy regimens had been the predominant approach in Europe and the US, based on pivotal phase III trials including the MAGIC study. Results from more recent landmark studies including the German FLOT4 and the Asian CLASSIC trials have, however, triggered a shift from cisplatin towards oxaliplatin-based chemotherapy protocols in the perioperative setting. Areas covered: This drug profile summarizes current state-of-the-art of perioperative and adjuvant treatment for locally advanced resectable gastric/GEJ cancers with a special focus on the increasingly predominant role of oxaliplatin over cisplatin in this setting. We review pharmacology, clinical efficacy, and safety profile of oxaliplatin and oxaliplatin combination regimens. We highlight recent advances and ongoing developments in the field. Expert opinion: While the adoption of oxaliplatin-containing combination regimens for perioperative therapy of gastric/GEJ cancers represents a significant step ahead, many pivotal questions remain unanswered. At the sample time, the evolution of molecular subtyping and immunotherapy is likely to dramatically change clinical practice in the foreseeable future. [ABSTRACT FROM AUTHOR]

Chemotherapy-Related Cognitive Impairment (CRCI) can be an adverse effect in women treated for breast cancer. Some longitudinal studies reported deficits in attention, memory, and executive function following treatment, but other studies did not find cognitive changes. It is known that practice effects (PE) on repeated assessments with cognitive tests contribute to the discrepancies in these results, but its influence on scores has not been systematically explored. The present study examines the impact of PE on retest scores in a group of women with breast cancer treated with chemotherapy and evaluated longitudinally. Method: 51 women with breast cancer treated with a combination of 5-fluorouracil, epirubicin, and cyclophosphamide with or without taxanes were assessed after surgery but before chemotherapy (T1), post-chemotherapy (T2), and at one year after T2 (T3). Longitudinal changes on cognitive performance were analyzed twice: when retest scores were not corrected for PE and when correction for PE was applied to T2 and T3 scores. Results: When PE was not corrected, progressive improvement over time in measures of memory and divided attention at T2 and T3 was observed. In contrast, when PE was corrected, worsening was found in measures of memory, fluency, executive function, and attention at T2 and in attention and executive function at T3. Results after correction for PE are in line with previous longitudinal studies that report cognitive impairment after treatment with chemotherapy for breast cancer. Conclusion: Accounting for PE is recommended to identify true change on cognition through treatment with chemotherapy for breast cancer. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of the combined music and sleep hygiene education (COMMASH-E) intervention on the fatigue, sleep quality and functional status of children with cancer residing in temporary lodges in Indonesia. The design of this study was a quasi-experimental pre-post test with a control group. We recruited children with cancer aged 7–18 years (n = 58) using a consecutive sampling method and assigned them to intervention and control groups (n = 29 in each group). The intervention group had the COMMASH-E intervention while the control group received routine care. Fatigue, sleep quality and functional status were measured on days 1 and 4 using Allen's Fatigue in Childhood Cancer Scale, the Sleep Problem in Children Scale and the Barthel Index, respectively. T-dependent and independent tests and Multivariate Analysis of Covariance (MANCOVA) tests were performed for the data analysis. There were significant differences in fatigue, sleep quality and functional status between the intervention and control groups after the COMMASH-E intervention. Nonetheless, chemotherapy drugs contributed to the children's sleep quality. COMMASH-E was found to be more effective than routine care in the reducing fatigue and increasing the sleep quality and functional status of children with cancer. [ABSTRACT FROM AUTHOR]

Mucositis is a common and devastating side effect of chemotherapeutic agents in children undergoing chemotherapy. The prevention and management of mucositis are necessary to improve these children's quality of life. Oral care is a recommended strategy for preventing and managing oral mucositis. Thus, the objective of this study was to identify the relationship between oral care practice and mucositis incidence. A cross-sectional analytical design was used in this study. A total of 34 children from 3 to 12 years of age with acute lymphoblastic leukemia who were in the last cycle of chemotherapy were recruited through a snowball sampling method. The Oral Assessment Guide (OAG) was administered to assess the severity of mucositis. A majority of the participants (51.5%) had mucositis after completing the last cycle of chemotherapy. Furthermore, there was a statistically significant relationship between their oral care practice at home and mucositis incidence. These results show that oral care at home is linked with the incidence and severity of mucositis. Nurses should educate children with leukemia and their parents regarding good oral hygiene practice. [ABSTRACT FROM AUTHOR]

Understanding the effect of liposome size on tendency for accumulation in tumour tissue requires preparation of defined populations of different sized particles. However, controlling the size distributions without changing the lipid composition is difficult, and differences in compositions itself modify distribution behaviour. Here, a commercial microfluidic format as well as traditional methods was used to prepare doxorubicin-loaded liposomes of different size distributions but with the same lipid composition, and drug retention, biodistribution and localization in tumour tissues were evaluated. The small (∼50 nm diameter) liposomes prepared by microfluidics and large (∼75 nm diameter) liposomes displayed similar drug retention in in vitro release studies, and similar biodistribution patterns in tumour-bearing mice. However, the extent of extravasation was clearly dependent on size of the liposomes, with the small liposomes showing tissue distribution beyond the vascular area compared to the large liposomes. The use of microfluidics to prepare smaller size distribution liposomes compared to sonication methods is demonstrated, and allowed preparation of different size distribution drug carriers from the same lipid composition to enable new understanding of tissue distribution in compositionally consistent materials is demonstrated. [ABSTRACT FROM AUTHOR]

Background: Electrochemotherapy (ECT) is a cancer treatment modality where the intracellular accumulation of chemotherapeutic agents is enhanced by an applied electrical field. Aims/Objectives: To evaluate the long-term efficacy, safety and functional outcome after ECT treatment in high-risk non-melanoma skin cancer (NMSC) with curative intent. Materials and methods: Seven patients with SCC or BCC in the head and neck area were treated with ECT with intratumoral bleomycin administration. Results: Five patients were cured by ECT as a mono-modality treatment after a median 10-year follow-up period. Two patients had recurrences and/or persisting tumors after treatment that required salvage surgery and radiotherapy. In two patients, the eye was spared with no visual impairment. In another patient, full facial nerve function was spared. Conclusions: ECT can be a curative as well as an organ and function-sparing mono modality treatment in high-risk NMSC. Significance: Today ECT is mostly used as a palliative treatment. Its curative potential should be further investigated. Randomized studies comparing ECT with standard treatment is needed. Hopefully, this small study can encourage such studies. [ABSTRACT FROM AUTHOR]

The effects of therapy on avascular cancer development based on a stochastic cellular automata model are considered. Making the model more compatible with the biology of cancer, the following features are implemented: intrinsic resistance of cancerous cells along with drug-induced resistance, drug-sensitive cells, immune system. Results are reported for no treatment, discontinued treatment after only one cycle of chemotherapy, and periodic drug administration therapy modes. Growth fraction, necrotic fraction, and tumour volume are used as output parameters beside a 2-D graphical growth presentation. Periodic drug administration is more effective to inhibit the growth of tumours. The model has been validated by the verification of the simulation results using in vivo literature data. Considering immune cells makes the model more compatible with the biological realities. Beside targeting cancer cells, the model can also simulate the activation of the immune system to fight against cancer. Abbreviations CA: cellular automata; DSC: drug sensitive cell; DRC: drug resistant cell; GF: growth fraction; NF: necrotic fraction; ODE: ordinary differential equation; PDE: partial differential equation; SCAM: The proposed stochastic cellular automata model [ABSTRACT FROM AUTHOR]

Introduction: One aim of the long-term care in survivors from acute lymphoblastic leukemia (ALL) during childhood is to avoid or limit complications caused by aggressive therapeutic strategies. Areas covered: ALL survivors are a heterogeneous group according to therapeutic protocols. In the last decades, cranial radiotherapy (cRT) has been largely replaced by intrathecal chemotherapy (CT) with a reduction of endocrine sequelae. Published studies are generally difficult to be interpreted because patients were treated according to different risk-adapted protocols and results are conflicting. We perform this review on endocrine long-term effects in childhood ALL survivors focusing on studies published in the last decades. Articles were selected using the following terms (Mesh terms): 'acute lymphoblastic leukemia' AND 'survivors' AND 'childhood' AND 'growth/puberty/fertility/obesity/metabolic syndrome/bone'. Expert commentary: Most childhood ALL survivors treated with CT alone attain normal height and have adequate pubertal development. Despite recent protocols improvements, ALL survivors still develop long-term metabolic complications (overweight, obesity, and cardiovascular disease) especially the female gender and patients with an increased body mass index (BMI) at diagnosis. The aim of this review is to describe the state of the art on these topics. We should be able to anticipate, prevent, and treat endocrine long-term morbidities through a well-established follow-up strategy. [ABSTRACT FROM AUTHOR]

Background/Aims: Paclitaxel is largely used as a chemotherapeutic agent for the treatment of several types of cancers. However, one of the significant limiting complications of paclitaxel is painful peripheral neuropathy during its therapy. The purposes of this study were to examine (1) the effects of blocking mammalian target of rapamycin (mTOR) on mechanical and thermal hypersensitivity evoked by paclitaxel; and (2) the underlying mechanisms responsible for the role of mTOR in regulating paclitaxel-induced neuropathic pain. Methods: Behavioral test was performed to determine mechanical and thermal sensitivity in rats. ELISA was used to examine the levels of proinflammatory cytokines (PICs including IL-1β, IL-6, and TNF-α) and substance P and calcitonin gene-related peptide (CGRP) in the dorsal root ganglion (DGR); and Western blot analysis was used to examine expression of mTOR signal pathway. Results: Paclitaxel increased mechanical and thermal sensitivity as compared with vehicle control animals (P < 0.05 vs. controls). Paclitaxel also amplified the expression of p-mTOR, mTOR-mediated phosphorylation of p70 ribosomal S6 protein kinase 1 (p-S6K1), 4E-binding protein 1 (p-4E-BP1) in the DRG. Blocking mTOR using rapamycin attenuated peripheral painful neuropathy observed in paclitaxel rats (P < 0.05 vs. without rapamycin). This inhibitory effect was accompanied with decreases of IL-1β, IL-6, and TNF-α as well as substance P and CGRP. In addition, inhibition of phosphatidylinositide 3-kinase (p-PI3K) attenuated expression of p-mTOR and PICs/substance P/CGRP in paclitaxel rats and this further attenuated mechanical and thermal hypersensitivity. Conclusions: The data revealed specific signaling pathways leading to paclitaxel-induced peripheral neuropathic pain, including the activation of PI3K-mTOR, PIC signal, and substance P and CGRP. Inhibition of these pathways alleviates neuropathic pain. Targeting one or more of these molecular mediators may present new opportunities for treatment and management of neuropathic pain observed during chemotherapeutic application of paclitaxel. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer among women. Need for novel preventive and curative approaches with more safety than the present one seems inevitable. This review is devoted to potentially favorable role of probiotics in prevention and treatment of breast cancer as well as their alleviating role regarding chemotherapy-induced side effects. Literature was searched for human, animal, and in vitro studies about the role of probiotics in breast cancer. In vitro studies showed that probiotic intervention induces cancer cells apoptosis and inhibits their proliferation. In animal models, treatment with probiotics inhibited tumor growth and reduced tumor size; also, the immunomodulatory, antiangiogenesis and antimetastatic activities of probiotics were illustrated. Human studies showed that intake of Lactobacillus casei shirota reduced the breast cancer incidence and consumption of fermented milk products and yogurt was inversely associated with breast cancer incidence; however, no study regarding the curative role of probiotics in breast cancer is available. Studies on the effect of probiotics on chemotherapy-induced side effects in breast cancer were contradictory but showed potential for more investigation. Probiotics seem to have a potential role in both prevention and treatment of breast cancer. However, more clinical studies are needed to elucidate their efficacy and safety. [ABSTRACT FROM AUTHOR]

Objective: In pancreatic cancer, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of radio(chemo)therapy. The aim of this systematic review is to investigate the validity of the hypothesis that hyperthermia added to radiotherapy and/or chemotherapy improves treatment outcome for pancreatic cancer patients. Methods and materials: We searched MEDLINE and Embase, supplemented by handsearching, for clinical studies involving hyperthermia in pancreatic cancer patients. The quality of studies was evaluated using the Oxford Centre for Evidence-Based Medicine levels of evidence. Primary outcome was treatment efficacy; we calculated overall response rate and the weighted estimate of the population median overall survival (mp) and compared these between hyperthermia and control cohorts. Results: Overall, 14 studies were included, with 395 patients with locally advanced and/or metastatic pancreatic cancer of whom 248 received hyperthermia. Patients were treated with regional (n = 189), intraoperative (n = 39) or whole-body hyperthermia (n = 20), combined with chemotherapy, radiotherapy or both. Quality of the studies was low, with level of evidence 3 (five studies) and 4. The six studies including a control group showed a longer mp in the hyperthermia groups than in the control groups (11.7 vs. 5.6 months). Overall response rate, reported in three studies with a control group, was also better for the hyperthermia groups (43.9% vs. 35.3%). Conclusions: Hyperthermia, when added to chemotherapy and/or radiotherapy, may positively affect treatment outcome for patients with pancreatic cancer. However, the quality of the reviewed studies was limited and future randomised controlled trials are needed to establish efficacy. [ABSTRACT FROM AUTHOR]

Osteosarcoma is among the most common malignant bone tumors in human skeletal system. The conventional treatment of osteosarcoma mainly consists of combining neoadjuvant chemotherapy with surgical approach. However, it is crucial to design an artificial implant that possesses excellent biomechanical properties and is capable of sustaining local release of chemotherapeutics. In this study, we envision that the highly efficient combination of gemcitabine (GEM) hydrochloride loaded liposomes with gelatin methacryloyl (GelMA) of in situ photocrosslinkable hydrogel will lead to a multifunctional implant with unique antitumor, mechanical, and biodegradable properties. A sustained controlled release was observed; more specifically, the release of GEM in vitro lasted for 4 days long. Furthermore, its capability in killing MG63 cells was further explored by using the lixivium of GEM-Lip@Gel and GEM-GelMA hydrogel in vitro (composite hydrogel by GEM loaded liposomes blending with GelMA, short for GEM-Lip@Gel), which agreed with the drug release outcome. In addition, these hydrogel showed excellent ability in inhibiting osteosarcoma in vivo by Balb/c mice bearing MG63 cells. Therefore, GEM-loaded lipo-hydrogel certainly has presented itself as a promising strategy for the development of implant in the field of osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

Most antitumor ingredients found in nature have poor solubility. These ingredients are expected to have much better absorption and higher bioavailability than synthetic antitumor agents. Woody oil emulsive nanosystems carrying poorly soluble natural alkaloids were fabricated (evodiamine (EA) carried by fructus bruceae oil-based emulsive nanosystems, or EFEN). Fructus bruceae oil has two excipient-like properties (oil phase and stabilizer) that contribute to the formulation and one drug-like property (antitumor effects) that synergizes with the antitumor effect of EA. The properties of EFEN were compared with free EA, a blank nanoemulsion, an EA-loaded emulsive nanosystem, and a fructus bruceae oil-loaded emulsive nanosystem. For the first time, this suggests that increases in the sensitivity of lung cancer cells to poorly soluble natural alkaloids can be achieved by delivering drugs using woody oil-based emulsive nanosystems. In this study, woody oil-based emulsive nanosystems efficiently deliver poorly soluble natural alkaloids. [ABSTRACT FROM AUTHOR]

An estrogen (ES)-functionalized cationic liposomal system was developed and exploited for targeted delivery to osteosarcoma. Natural biocompatible chotooligosaccharides (COS, MW2-5 KDa) were covalently tethered to the liposomal surface through a disulfate bond (-SS-) to confer reduction-responsive COS detachment, whereas estrogen was grafted via polyethylene glycol (PEG 2 K) chain to achieve estrogen receptor-targeting. The liposomal carriers were prepared by the ethanol injection method and fluorescent anticancer drug doxorubicin (DOX) was loaded with ammonium sulfate gradient. The physicochemical properties, reduction-sensitivity, and the roles of estrogen on cellular uptake and tumor-targeting were studied. The Chol-SS-COS/ES/DOX liposomes were spherical with an average size about 110 nm, and high encapsulation efficiency. The liposomes were stable in physiological condition but rapidly release the payload in response to tumoral intracellular glutathione (20 mM). MTT cytotoxicity assay confirmed that Chol-SS-COS/ES/DOX liposomes exhibited higher cytotoxicity to MG63 osteosarcoma cells than to liver cells (LO2). Flow cytometry (FCM) and confocal laser scanning microscopy revealed that cellular uptake of Chol-SS-COS/ES/DOX liposomes by MG63, than the free DOX or Chol-SS-COS/DOX. Ex vivo fluorescence distribution study showed that the multifunctional liposomes selectively accumulated in the MG63 xenografts versus the organs. Chol-SS-COS/ES/DOX liposomes strongly inhibited the tumor growth and enhanced the animal survival rate. Overall, the COS grafted estrogen-functionalized cationic liposomes, fortified with glutathione-responsiveness, showed great potential for specific intracellular drug delivery to estrogen receptor-expressing tumors such as osteosarcoma. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most devastating primary brain tumor due to its infiltrating and diffuse growth characteristics, a situation compounded by the lack of effective treatments. Currently, many efforts are being devoted to find novel formulations to treat this disease, specifically in the nanomedicine field. However, due to the lack of comprehensive characterization that leads to insufficient data on reproducibility, only a reduced number of nanomedicines have reached clinical phases. In this context, the aim of the present study was to use a cascade of assays that evaluate from physical-chemical and structural properties to biological characteristics, both in vitro and in vivo, and also to check the performance of nanoparticles for glioma therapy. An amphiphilic block copolymer, composed of polyester and poly(ethylene glycol; PEG) blocks, has been synthesized. Using a mixture of this copolymer and a polymer containing an active targeting moiety to the Blood Brain Barrier (BBB; Seq12 peptide), biocompatible and biodegradable polymeric nanoparticles have been prepared and extensively characterized. In vitro studies demonstrated that nanoparticles are safe for normal cells but cytotoxic for cancer cells. In vivo studies in mice demonstrated the ability of the Seq12 peptide to cross the BBB. Finally, in vivo efficacy studies using a human tumor model in SCID mice resulted in a significant 50% life-span increase, as compared with non-treated animals. Altogether, this assay cascade provided extensive pre-clinical characterization of our polymeric nanoparticles, now ready for clinical evaluation. [ABSTRACT FROM AUTHOR]

Gestational trophoblastic neoplasia (GTN) can result from the over-proliferation of trophoblasts. Treatment of choriocarcinoma, the most aggressive GTN, currently requires high doses of systemic chemotherapeutic agents, which result in indiscriminate drug distribution and severe toxicity. To overcome these disadvantages and enhance the chemotherapeutic efficacy, chondroitin sulfate A (CSA)-binding nanoparticles were developed for the targeted delivery of doxorubicin (DOX) to choriocarcinoma cells using a synthetic CSA-binding peptide (CSA-BP), derived from malarial protein, which specifically binds to the CSA exclusively expressed in the placental trophoblast. CSA-BP-conjugated nanoparticles rapidly bonded to choriocarcinoma (JEG3) cells and were efficiently internalized into the lysosomes. Moreover, CSA-BP modification significantly increased the anti-cancer activity of the DOX-loaded nanoparticles in vitro. Intravenous injections of CSA-BP-conjugated nanoparticles loaded with indocyanine green (CSA-INPs) were rapidly localized to the tumor. The CSA-targeted nanoparticles loaded with DOX (CSA-DNPs) strongly inhibited primary tumor growth and, more importantly, significantly suppressed metastasis in vivo. Collectively, our results highlight the potential of the CSA-BP-decorated nanoparticles as an alternative targeted delivery system of chemotherapeutic agents for treating choriocarcinoma and for developing new GTN therapies based on drug targeting. [ABSTRACT FROM AUTHOR]

Introduction: In recent decades, adjuvant therapy has secured a firm position in the treatment of gastric cancer by improving patient prognosis. Currently, standard therapy varies between East Asia, Europe and North America due to heterogeneities of the tumor, race, medical environment and/or surgical procedure. Although adjuvant strategies, proved effective in each region and implemented to clinical practice, certain patient populations with advanced gastric cancer show recurrence and a fatal prognosis. The development of a universal adjuvant therapy with a high efficacy and acceptable adverse events or with less toxicity and non-inferiority seems to have become urgent and imperative. Areas covered: In this review, we aimed to summarize the current knowledge regarding adjuvant therapies for gastric cancer, including chemotherapy, chemoradiotherapy and molecular targeted therapy, based on clinical trials and to introduce the pivotal ongoing phase III trials. Expert commentary: The efficacy of adjuvant therapy to prevent recurrence remains insufficient although several trials have shown a significant benefit in patients with localized advanced gastric cancer. The development of more effective and universal multimodal adjuvant therapy is required. [ABSTRACT FROM AUTHOR]

Purpose: Central nervous system (CNS) prophylaxis in the treatment of childhood acute lymphoblastic leukaemia (ALL) is routinely achieved through intrathecal chemotherapy (ITC). The presence of high level language deficits in older children who received CNS-directed ITC for ALL in early childhood is yet to be elucidated, with previous research suggesting that high level language deficits may appear later in ALL survivors’ development at an age when these skills typically emerge. Method: A test battery covering foundational language skills and higher-order language skills was administered to five participants (aged 10-15 years) with a history of ITC for ALL. Conversion of each child’s language performance scores to z scores allowed for clinical interpretation of data across the language areas tested. Result: Foundational language skills were, in general, of no clinical concern. Three of the five children presented with clinically impaired language skills in areas including resolving ambiguity, making inferences and composing novel sentences. Performance variation between the participants and within the individual participants was noted. Conclusion: Given the importance of early adolescent language abilities to academic and social development in late primary and secondary schooling, these preliminary findings suggest further research into emerging adolescent language abilities following ITC for ALL is warranted. [ABSTRACT FROM AUTHOR]

Introduction: The field of transcatheter aortic valve implantation (TAVI) has seen an exponential expansion in TAVI devices for the treatment of severe symptomatic aortic stenosis. Areas covered: The ACURATE neo (Boston Scientific, MA, USA) is a second-generation self-expanding transcatheter aortic valve system. The valve presents a supra-annular design, and comprises three stabilization arches for axial alignment, an upper-crown for capping the aortic annulus, and a lowercrown that is opened over the native aortic valve for full deployment. This device minimally protrudes into the left ventricular outflow-tract, thereby minimizing the risk of conduction abnormalities. The ACURATE neo can be delivered by transfemoral and transapical approaches with a unique 'top-down' deployment. Information was gathered from published manuscripts obtained using standard databases (MEDLINE) and trial data presented at conferences. Expert commentary: Data from observational series show that TAVI with the ACURATE neo is associated with low rates of all-cause mortality, paravalvular leak, and permanent pacemaker requirement. Randomized data comparing the ACURATE neo valve with contemporary valves and long-term durability data are awaited. Continuing modifications in device and delivery system design are anticipated with a view to further reduction in paravalvular leak. [ABSTRACT FROM AUTHOR]

Background: Impact of time to start first-line systemic chemotherapy following diagnosis of metastatic colorectal cancer (mCRC) needs to be studied. Methods: This is a pooled analysis of the raw data of the comparator arms of two randomized studies (NCT00272051; NCT00305188). Univariate and multivariate analyses of predictors of overall and progression-free survival were conducted through Cox regression analysis. Factors with statistically significant P value (P < 0.05) in the univariate part of the analysis were included in the multivariate analysis. Results: In univariate analysis, time to start systemic therapy did not affect overall or progression-free survival (P=0.694; P= 0.891 respectively). In multivariate analysis for overall survival, the following factors were predictive of worse overall survival: younger age (P = 0.019), higher ECOG performance score (P = 0.001), more than one site of metastatic disease (P = 0.002), colon site of the primary tumor (P = 0.004), and no oncologic surgery to the primary tumor (P < 0.001). Likewise, in multivariate analysis for progression-free survival, the following factors were predictive of worse progression-free survival: no oncologic surgery to the primary (P < 0.001), more than one organ of metastatic disease (P < 0.001), and no concurrent bevacizumab administration (P = 0.015). Conclusion: Time to start systemic chemotherapy does not appear to impact overall or progression-free survival among mCRC patients. [ABSTRACT FROM AUTHOR]

Activating mutations in FMS-like tyrosine kinase 3 (FLT3), including internal tandem duplications (ITDs) and tyrosine kinase domain (TKD) mutations, are common in patients with acute myeloid leukemia (AML). FLT3-ITD is a negative prognostic factor that remains prognostically relevant even after intensive chemotherapy and/or stem cell transplant. FLT3 testing was historically viewed as being purely prognostic; however, with the advent of FLT3 inhibitors, it will likely be seen as both prognostic and predictive. The multikinase inhibitor midostaurin, in combination with chemotherapy, is the first targeted agent to significantly prolong survival in patients with newly diagnosed FLT3-mutated AML and was recently approved by health authorities. Recently, the European LeukemiaNet recommended FLT3 testing (both TKD and ITD) for all patients with AML, with results required within 3 days. The need for optimized, multigene platform testing incorporating FLT3 mutations will increase as knowledge of interactions between FLT3 and other myeloid-relevant mutations grows. [ABSTRACT FROM AUTHOR]

In this thematic narrative analysis, I examine how three young adult (YA) cancer survivors use humor and the five functions of illness-related storytelling in personal blogs maintained across the cancer trajectory to describe and counter their age-distinct biographical disruption. In 370 blog entries, YA narrators employed humor to facilitate biographical reconstruction and achieve "aligning moments" with audiences. Researchers and practitioners can use YA blogs to better understand the interpersonal health communication challenges associated with medical decision-making, altered social identities, the "void" following the completion of primary treatment, uncertainty about disclosure, and social isolation from other YA survivors. [ABSTRACT FROM AUTHOR]

This is a case of Ms. C, a 37-year-old woman originally from Zambia, Africa, with an unremarkable medical history prior to the unfortunate diagnosis of cervical cancer in 2014. Ms. C, was diagnosed with cervical cancer at an early stage with many treatment options available at the time of her diagnosis to potentially limit disease progression. Such therapeutic options included: conventional surgery, chemotherapy and radiation therapy, all commonly recognized treatment approaches for medical management, utilizing 'westernized' medicinal theories. Based upon the ideology of the patient's family and her own personal beliefs of healing and western medical practices, she instead opted for a culturally based complementary and alternative medicine (CAM) management of her cervical cancer and declined surgery, chemotherapy and radiation therapy. After 2 years of CAM management, her cervical cancer metastasized to her lungs and brain. After numerous hospitalizations for cancer-related illnesses and increasing symptom burden, she sought typical western medical interventions including chemotherapy, external beam radiation, along with a nephrostomy tube for renal failure and uterine artery embolization for chronic uterine bleeding. Within 6 months of such interventional techniques failing to improve her prognosis, the patient died under hospice home care. This case highlights the importance of elucidating how a patient understands their own medical condition and reconcile their belief system and cultural practices early in the management and treatment process. This is possible through emphasizing and practicing a thorough cross-cultural interview and is especially important when dealing with potentially life limiting pathologies like cancer, and when making key decisions such as choosing between CAM vs. western medicinal practices, or a holistic approach utilizing both. Physicians and patients must focus on removing cultural barriers to medical care. [ABSTRACT FROM AUTHOR]

Introduction: Primary Apocrine adenocarcinomas (PAA) are very infrequent tumors that are often confused initially with benign lesions. Little is known about this disease and there is still much to be clarified. We present a case of PAA on the eyelid successfully treated with surgery alone and a literature review regarding what is currently described about this disease. Methods: Noncomparative, retrospective case report of a patient with PAA on the eyelid succesfully treated with surgery alone and a literautre review. Results: A 91-year-old man with a 2 months lesion on the upper left eyelid was treated with surgery alone with oncological margins of 5mm. The Hystopathology diagnosis was a PAA of the eyelid and free margins were obtained. After 12 months of follow-up, the patient does not show any signs of local recurrence or distant metastasis. A review of the literature suggests these tumors are located more frequently in the axilla (50%) and secondly in the head and neck (35%), with similar distribution in the upper (41%) and lower eyelid (45%). The most commonly used treatment is surgical excision, but radiotherapy and chemotherapy have also been used with variable results. Conclusions: PAA is a very rare and aggressive tumor. Because it is so infrequent, treatments are based on the sporadic cases encountered in the literature. As more cases are reported, more can be elucidated about the characteristics of this tumor, its behavior and best treatment choice and this may allow progress in the understanding and management of this disease. [ABSTRACT FROM AUTHOR]

Objectives: To promote establishment of effective ototoxicity monitoring programs (OMPs), this report reviews the U.S. national audiology guidelines in relation to ''real world'' OMP application. Background is provided on the mechanisms, risks and clinical presentation of hearing loss associated with major classes of ototoxic medications. Design: This is a non-systematic review using PubMed, national and international agency websites, personal communications between ototoxicity experts, and results of unpublished research. Examples are provided of OMPs in various healthcare settings within the U.S. civilian sector, Department of Defense (DoD), and Department of Veterans Affairs (VA). Study Sample: The five OMPs compared in this report represent a convenience sample of the programs with which the authors are affiliated. Their opinions were elicited via two semi-structured teleconferences on barriers and facilitators of OMP, followed by a self-administered questionnaire on OMP characteristics and practices, with responses synthesized herein. Preliminary results are provided from an ongoing VA clinical trial at one of these OMP sites. Participants were 40 VA patients who received cisplatin chemotherapy in 2014--2017. The study arms contrast access to care for OMP delivered on the treatment unit versus usual care as provided in the audiology clinic. Results: Protocols of the OMPs examined varied, reflecting their diverse settings. Service delivery concerns included baseline tests missed or completed after the initial treatment, and monitoring tests done infrequently or only after cessation of treatment. Perceived barriers involved logistics related to accessing and testing patients, such as a lack of processes to help patients enter programs, patients' time and scheduling constraints, and inconvenient audiology clinic locations. Use of abbreviated or screening methods facilitated monitoring. Conclusions: The most effective OMPs integrated audiological management into care pathways of the clinical specialties that prescribe ototoxic medications. More OMP guidance is needed to inform evaluation schedules, outcome reporting, and determination of actionable ototoxic changes. Guidance is also lacking on the use of hearing conservation approaches suitable for the mass testing needed to support large-scale OMP efforts. Guideline adherence might improve with formal endorsement from organizations governing the medical specialty stakeholders in OMP such as oncologists, pulmonologists, infectious disease specialists, ototolaryngologists and pharmacists. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine the feasibility of using nanoparticle-enhanced transmission ultrasound (NETUS) as an image-based monitoring modality for microwave hyperthermia treatment. Methods: A dedicated transmission ultrasound imaging system was used to obtain acoustic projections and ultrasound computed tomography images. Initially, speed-of-sound based images were used to non-invasively monitor temperature changes in in vitro and ex vivo specimens, induced by a microwave needle-type applicator. Next, the hyperthermia acceleration ability of two ultrasound nanoparticles based contrast agents (iron oxide and copper oxide) was examined and visualised. Finally, a two-step image guided microwave therapeutic procedure using NETUS was investigated in a realistic breast mimicking phantom. First, the pathology simulating region borders were detected. Then, a microwave-induced temperature elevation was non-invasively monitored. Results: The transmission ultrasound scanning system was able to detect temperature changes with a resolution of less than 0.5 °C, both in vitro and ex vivo. In accordance with previous studies, it was visually demonstrated that iron oxide nanoparticles expedite the heating process (p < 0.05). Copper oxide nanoparticles, however, did not alter the hyperthermia profile significantly. In the breast mimicking phantom, NETUS yielded accurate detection of the target region as well as thermal monitoring of the microwave heating procedure. Conclusions: NETUS can combine enhanced target visualisation with non-invasive thermometry and accelerated heating effect. Quantitative feedback, however, requires a tissue-specific calibration-curve. A proof of concept for microwave hyperthermia treatment monitoring using NETUS was established. The suggested methodology may potentially provide a non-invasive cost-effective means for monitoring thermal treatment of the breast. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we investigated the differences in hyperthermia treatment (HT) quality between treatments applied with different hyperthermia systems for sub-superficial tumours in the head and neck (H&N) region. Materials and methods: In 24 patients, with a clinical target volume (CTV) extending up to 6 cm from the surface, we retrospectively analysed the predicted HT quality achievable by two planar applicator arrays or one phased-array hyperthermia system. Hereto, we calculated and compared the specific absorption rate (SAR) and temperature distribution coverage of the CTV and gross tumour volume (GTV) for the Lucite cone applicator (LCA: planar), current sheet applicator (CSA: planar) and the HYPERcollar (phased-array). Results: The HYPERcollar provides better SAR coverage than planar applicators if the target region is fully enclosed by its applicator frame. For targets extending outside the HYPERcollar frame, sufficient SAR coverage (25% target coverage, i.e. TC25 ≥ 75%) can still be achieved using the LCA when the target is fully under the LCA aperture and not deeper than 50 mm from the patient surface. Conclusion: Simulations predict that the HYPERcollar (hence also its successor the HYPERcollar3D) is to be preferred over planar applicators such as LCA and current sheet applicator in sub-superficial tumours in the H&N region when used within specifications. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy of percutaneous thermal ablation in treating colorectal cancer liver metastases (CRCLM), and to propose a prognostic nomogram for overall survival (OS). Materials and methods: Seventy-one patients with CRCLM undergoing thermal ablation at our institute from 2009 to 2013 were identified and analysed to formulate a prognostic nomogram. The concordance index (C-index) and calibration curve were calculated to evaluate the predictive accuracy of the nomogram. The nomogram was compared with two current prognostic nomograms for patients with CRCLM who had undergone hepatectomy (Kattan) and selective internal radiation therapy (Fendler). Predictive validity was assessed in the validation cohort of 25 patients who had undergone thermal ablation from 2014 to 2016. Results: The median OS in the primary cohort was 26.4 months, whereas the 1-, 3- and 5-year OS rates were 72.2%, 37.2% and 17%, respectively. The median progression-free survival was 4.2 months. After univariate and multivariate analysis, a prognostic nomogram was formulated based on four predictors, including the number of tumours, maximum diameter of the tumour, CA19-9 level and ablation margin. The C-index of the nomogram was 0.815. Based on the patients of this study, the C-index was significantly higher than that of the Fendler nomogram (C-index, 0.698) and Kattan nomogram (C-index, 0.514, p < 0.001). Predictive accuracy of the proposed nomogram was also satisfactory in the validation cohort, with a C-index of 0.884. Conclusions: Thermal ablation was an effective therapy for CRCLM. Moreover, the nomogram was effective and simple for CRCLM patients undergoing thermal ablation. [ABSTRACT FROM AUTHOR]

1.YMR-65, 5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3-methoxyphenyl)-4, 5-dihydro-1H-pyrazole-1-carboxamide, is a new tubulin polymerization inhibitor with encouraging anticancer activity. 2.The validated ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) method was successfully applied to the pharmacokinetics, tissue distribution and excretion study of YMR-65 after oral and intravenous administration. The area under concentration-time curve (AUC0-∞) for YMR-65 were 151.67 ± 54.48 and 459.45 ± 49.23 ng/ml*h for oral and intravenous administration at the dosage of 1.5 mg/kg, respectively and the oral bioavailability was about 33.01%. Moreover, YMR-65 was extensively distributed in heart, liver, spleen, lung, kidney, stomach, intestine and testis and the highest were detected in heart, followed by stomach, intestine and liver. The majority of YMR-65 was excreted via feces and its accumulative excretion ratio during the period of 96 h was 19.83 ± 3.01%, but only 1.54 ± 0.37 and 0.215 ± 0.026% for urine within 96 h and bile within 10 h after intravenous administration, respectively, though the fecal and urine excretion were incomplete within 96 h. 3.In summary, this study defined the pharmacokinetic characteristics of YMR-65 in vivo and the important data can be a useful resource for further research and development. [ABSTRACT FROM AUTHOR]

Two new 13,14:14,15-disecopregnane-type C21 steroidal glycosides, namely komarosides R (1) and S (2), along with four known compounds (3-6), were obtained from the 95% ethanol extract of the whole herbs of Cynanchum komarovii Al.Iljinski (Asclepiadaceae). The structures of new compounds were elucidated on the basis of 1D, 2D NMR spectroscopic data and acid hydrolysis. Compounds 1 and 2 showed potent inhibitory activities against human leukemia cell line (HL-60) with IC50 values being 6.2 and 17.6 μM, respectively, compared to the positive control 5-fluorouracil (6.4 μM). [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) defies the currently practiced management of radiotherapy, chemotherapy and surgery and hence, it is associated with a high fatality rate with a median survival of 14.6 months. In our previous work investigating different tyrosine kinase inhibitors (TKIs), we established that a combination of Crizotinib and Dasatinib exerted the most potent effect on different GBM cell lines. In this work, to improve targeted therapy at the site of the tumour and avoid systemic toxicity, we exploited the enhanced permeability and retention effect by designing micellar formulations of these two TKIs. Crizotinib and Dasatinib were successfully encapsulated in poly(styrene-co-maleic acid) (SMA) micelles which were then evaluated for their physicochemical characteristics, anti-proliferative effect, mode of cell death, efficacy in spheroid models, effect on cell signalling, antiangiogenic potential and in vivo anticancer activity. Our results showed that this combination had induced a potent anti-proliferative effect in four GBM cell lines grown as a monolayer and as a spheroid. The combination was also efficacious in in vitro models of angiogenesis and vascular mimicry. In vivo data showed the enhanced activity of the micellar TKIs compared to free drugs. In conclusion, we proved that micellar formulations of Crizotinib and Dasatinib carry promising in vitro and in vivo efficacy that warrant further investigation. [ABSTRACT FROM AUTHOR]

Today, intratumoural heterogeneity has been recognised as one of the main causes of cancer treatment failure and drug resistance development through which multiple mechanisms are simultaneously involved. From the broad diversity of cells presented in tumour microenvironment, owing to their proliferative potential and longevity, cancer stem cells (CSCs), are the main cell subpopulation involved in tumour development, propagation, metastatic dissemination and induction of intratumoural heterogeneity. Accordingly, selective targeting and eradication of CSCs may represent a promising approach for cancer therapy and evading drug resistance development. Nanotechnology is an attractive outgrowing field in medicine due to its promising capabilities in solving several obstacles associated with conventional chemotherapy agents including poor solubility, lack of selectivity and high systemic toxicity. Accordingly, multiple types of nanocarriers have been successfully developed for improving selective delivery and reducing non-selective toxicities of CSC-specific chemotherapy agents. In Current review, we mostly focus on examining the role of CSCs in development of intratumoral heterogeneity and introducing recently developed nano delivery systems for more efficient targeting and eradication of them. [ABSTRACT FROM AUTHOR]

Objective: We observed that ph + ALL patients administrated with recombinant human G-CSF (rhG-CSF) after intense chemotherapy have presented a trend of disease relapse. Thus, we aim to thoroughly investigate the expression and role of GM-CSFR and G-CSFR on ph + ALL patients. Method: SUP-B15, BALL-1 and primary leukemia cells were used in this study. Transcript levels were analyzed by quantitative PCR while cell viability was measured using a CCK-8 assay. Flow cytometry was used to assess the different stages of cell cycle. Results: We found that the mRNA expression levels of GM-CSFR and G-CSFR were higher in patients with ph + ALL, as well as in SUP-B15 cells. rhG-CSF was also observed to promote the viability of SUP-B15 cells while inversely inhibiting BALL-1 cell viability. In addition, we also determined that rhG-CSF (100 ng/ml) decreased the sensitivity of SUP-B15 cells to imatinib and nilotinib, while the results were exactly the contrary for dasatinib. Conclusion: We demonstrated high expression levels of GM-CSFR and G-CSFR, as well as their promotable role for viability in ph + ALL cells. We further found that rhG-CSF influenced the sensitivity of SUP-B15 cells to TKIs. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, the prognosis for low-grade lymphoma in the ocular region has improved markedly, whereas high-grade lymphoma is still a challenging disease to manage. Numerous strategies are available for treating ocular adnexal lymphoma, and these include chemotherapy, radiotherapy, and immune-modulating agents. Areas covered: This review provides an overview of the available treatment modalities for ocular adnexal lymphoma, including novel treatment approaches and recent advances. Furthermore, management guidelines for ocular adnexal lymphoma are provided based on existing guidelines described for lymphoma outside the ocular region. This review was based on an extensive MEDLINE search using keywords such as ‘Ocular adnexal lymphoma AND treatment’, ‘Ocular adnexal lymphoma AND management’. Expert commentary: Ocular adnexal lymphoma is a rare disease and the treatment modalities of ocular adnexal lymphoma are numerous. Therefore, we suggest that the treatment should be centralized in centers in each country and placed in a small number of experienced hands. This, in combination with large multicenter studies, will provide new information and improve the prognosis in the future. The treatment of low-grade low-stage lymphoma mainly includes radiotherapy alone. High-stage or high-grade lymphoma should be managed with chemotherapy or immunochemotherapy, potentially in combination with radiotherapy. In recent years, many new therapy approaches have occurred, and expectations for therapies such as chimeric antigen receptor-modified T-cells are high. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Within ALL, precursor B-cell disease predominates and now has survival >90%. Mature B-cell, or Burkitt leukemia/lymphoma, is distinct from ALL and requires short intensive chemotherapy and with the addition of Rituximab, survival rates of >95% are achieved. Its defining characteristic is MYC translocation at 8q24. Patients who have features of both ALL and Burkitt leukemia/lymphoma represent a rare subpopulation of ALL and present a diagnostic and treatment conundrum. We have performed a systematic review on the occurrence of and treatment of MYC positive precursor B-ALL, reported between 1980 and 2016. The review highlighted a lack of data to guide any consensus about how to treat this important group of children and focused research in this area is needed. [ABSTRACT FROM AUTHOR]