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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

This study aimed to investigate the mechanisms of a combined brief cognitive behavioral plus bright light therapy (CBT-I+Light) in women receiving chemotherapy. Women (N = 101) were randomly assigned to CBT-I+Light or treatment as usual plus relaxation audios (TAU+). Participants completed sleep diaries and wore an actigraph during the 6-week intervention period. Patient-reported outcomes were assessed at baseline, mid-point (week 3), and later (week 6). Cognitive (i.e., dysfunctional sleep beliefs, pre-sleep cognitions, and arousal) and behavioral (i.e., time in bed awake and day-to-day out-of-bedtime variability) mechanisms were examined. Cognitively, both groups declined significantly in overall dysfunctional sleep beliefs from pre- to post-intervention (both p<.04); however, they did not differ on sleep-related beliefs nor pre-sleep cognitions and arousal at post-intervention (both p>.50). Dysfunctional beliefs sleep expectations subscale was lower in CBT-I+Light versus TAU+ (p=.01). Behaviorally, CBT-I+Light reported less overall time in bed awake after the start of the intervention (p<.05) and significantly less time in bed during the morning until the final week of the intervention period. Out-of-bedtime day-to-day variability was lower in the CBT-+Light vs TAU+ at the final intervention day. Mechanisms of CBT-I+Light during chemotherapy remain to be shown. Our results suggest that changes in behavioral mechanisms may be associated with sleep improvements within this cohort. Future studies should assess the role of additional mechanisms (e.g., sleep effort) within larger samples. Whilst intervention brevity is important, more potent interventions may be required to achieve robust changes in target mechanisms. [ABSTRACT FROM AUTHOR]

Liver-dominant metastatic colorectal cancer is noted in approximately 20%–35% of the patients. Systemic chemotherapy remains the first-line treatment for mCRC, but the prognosis is poor due to liver failure. Novel minimally invasive technologies have enabled the optimization of locoregional treatment options. This is a comprehensive review of novel locoregional treatment technologies, both percutaneous ablation and transcatheter arterial treatments, which can be used to decrease hepatic disease progression in patients with mCRC. Trans-arterial radioembolization is the most recently developed locoregional treatment for metastatic liver disease, and robust evidence has been accumulated over the past years. Image-guided techniques, endovascular and ablative, have gained wide acceptance for the treatment of liver malignancies, in selected patients with non-resectable disease. The optimization of dosimetry and microsphere technological advancement will certainly upgrade the role of liver radioembolization segmentectomy or lobectomy in the upcoming years, due to its curative intent. Also, ablative interventions provide local curative intent, offering significant and sustained local tumor control. Standardization protocols in terms of predictability and reliability using immediate treatment assessment and ablation zone software could further ameliorate clinical outcomes. [ABSTRACT FROM AUTHOR]

Optimal chemotherapy management is substandard in low and middle-income countries. We aimed to identify major gaps to design interventional strategies for improved chemotherapy management at Tikur Anbessa Specialized Hospital (TASH), Ethiopia. This study was conducted using an observational checklist, open-ended questions, record review, and key informant interviews of department heads and focal persons at TASH. Findings were categorized into specific themes that developed. Chemotherapy represented 60.2% of the hospital medication budget. Drug utilization was quantified via monthly consumption documentation and forecasting. However, unreliable data resulted in frequent stockouts (unavailability of the item when it is needed) of chemotherapy with only 67.8% availability. Thirteen healthcare personnel (9 nurses, 2 pharmacists and 2 hospital cleaners) were interviewed: all clinical staff but neither of hospital cleaners believed that they were at risk of hazardous agents. Challenges identified included inadequate and frequent stockouts (unavailability of the item when it is needed) of personal protective equipment, lack of standardized guidelines for chemotherapy handling, admixture, and disposal, lack of designated preparation rooms, and lack of training. All nine nurses handled chemotherapy admixtures despite only two nurses previously receiving in-service training. Most of the participants had never witnessed the disposal of anticancer drugs. Prompted by the results of this study, a dialogue was initiated among members of TASH, the American Cancer Society and the University of North Carolina to implement action-oriented projects to address the gaps identified at TASH. These gaps directly and indirectly affect care and treatment outcomes of patients at a large cancer center. Collaborations with well-resourced centers are potential models for improving chemotherapy management. [ABSTRACT FROM AUTHOR]

This guideline has been developed jointly by the European Society of Haematology and International Society of Amyloidosis recommending non-transplant chemotherapy treatment for patients with AL amyloidosis. A review of literature and grading of evidence as well as expert recommendations by the ESH and ISA guideline committees. The recommendations of this committee suggest that treatment follows the clinical presentation which determines treatment tolerance tempered by potential side effects to select and modify use of drugs in AL amyloidosis. All patients with AL amyloidosis should be considered for clinical trials where available. Daratumumab-VCD is recommended from most untreated patients (VCD or VMDex if daratumumab is unavailable). At relapse, the two guiding principles are the depth and duration of initial response, use of a class of agents not previously exposed as well as the limitation imposed by patients' fitness/frailty and end organ damage. Targeted agents like venetoclax need urgent prospective evaluation. Future prospective trials should include advanced stage patients to allow for evidence-based treatment decisions. Therapies targeting amyloid fibrils or those reducing the proteotoxicity of amyloidogenic light chains/oligomers are urgently needed. [ABSTRACT FROM AUTHOR]

Malignant bowel obstruction is a common complication of advanced gastrointestinal, gynecologic, and genitourinary tumors. Patients present with nausea, vomiting, abdominal pain, and constipation. Cross-sectional imaging is essential to make a diagnosis of bowel obstruction. Initial management is conservative with fluid replacement, electrolyte replacement, bowel rest and sometimes nasogastric decompression. Numerous advanced options exist for definitive management, though none are overly promising but nevertheless may improve quality and quantity of life. Surgical bypass, endoscopic stenting, and endoscopic decompression are some of the options with variable efficacy and are employed in select patients. Chemotherapy may be utilized if the bowel obstruction resolves to reduce tumor burden in a limited number of patients. Parenteral nutrition is an option and should typically be used in surgical patients with good functional and nutritional status with limited tumor burden or curative intent. Palliative care and hospice should be discussed in patients with advanced malignancy who present with peritoneal carcinomatosis or multiple levels of obstruction. Overall prognosis of malignant bowel obstruction is poor, and median survival ranges from 26 to 192 days. [ABSTRACT FROM AUTHOR]

The article responds to "Comprehensive Diagnosis and Management of Malignant Bowel Obstruction: A Review" and addresses key controversies and omissions in the management of malignant bowel obstruction (MBO). It challenges certain recommendations in the original article, such as the use of metoclopramide and ondansetron, highlighting the need for a more rigorous assessment of available evidence and consideration of uncertainties in palliative care for MBO.

Uveal melanoma (UM) is the common primary cancer of the eye and new treatments are needed. Substantial evidence has shown that an antibiotic monensin is an attractive candidate for the development of anti-cancer drug. In this study, we investigated the potential of repositioning monensin for the treatment of UM in the pre-clinical setting. Cellular activity assays were performed using multiple cell lines representing UM models with different cellular origins and genetic profiling and normal cells as control. Combination studies were performed using Chou-Talalay method. Mechanism studies were performed using immunoblotting and ELISA. Monensin was effective against all tested UM cell lines and less effective against normal fibroblast cells. Monensin induced G0/G1 arrest and thus decreased S phase, leading to UM cell growth inhibition. It also inhibited migration and induced apoptosis in UM cells. In addition, the combination of monensin and dacarbazine was synergistic in targeting UM cells. Our mechanistic studies showed that monensin specifically decreased activity of RhoA without affecting other small GTPases, such as Ras and Rac1. Consistently, monensin decreased phosphorylation of downstream effectors of RhoA signaling, including ROCK, MYPT1 and MLC. Rescue studies using RhoA activator calpeptin showed that calpeptin significantly abolished the inhibitory effects of monensin on RhoA activity, proliferation, migration and survival, confirming that RhoA is the target of monensin in UM cells. Our study demonstrates that monensin is a potent inhibitor of UM and synergizes with chemotherapy, via suppressing RhoA activity and RhoA-mediated signaling. Our findings suggest that monensin may be a potential lead compound for further development into a drug for UM treatment. [ABSTRACT FROM AUTHOR]

Individuals with cancer often present food aversion after initiation of anti-tumor treatment, which may impair nutritional status. We aim to assess the prevalence and factors associated with food aversion during cancer treatment. Articles from three databases were searched: MEDLINE, EMBASE and Cochrane Library. English was used, with no restriction on the year of publication. Inclusion criteria were original articles that evaluated food aversion in adults and the elderly undergoing chemotherapy and/or radiotherapy treatment. Fifteen articles were included. A high prevalence of food aversion (21–62%) was observed, with meat considered the most aversive food. The aversion is usually transient and may be due to gastrointestinal problems, such as nausea and vomiting, caused by chemotherapy or radiotherapy treatment, and even psychological and emotional issues. Offering a new food before the beginning of treatment seems to be an effective strategy to reduce aversion, combined with nutritional and psychological monitoring. Cancer patients have a high prevalence of food aversion. Multidisciplinary care can minimize the consequences of cancer treatment. [ABSTRACT FROM AUTHOR]

To assess the cost-effectiveness of transarterial radioembolization (TARE) versus conventional transarterial chemoembolization (cTACE) and drug-eluting beads chemoembolization (DEE-TACE) for patients with unresectable early- to intermediate-stage hepatocellular carcinoma (HCC). A cohort-based Markov model with a five-year time horizon was developed to evaluate the cost-effectiveness of the three embolization treatments. Upon entering the model, patients with HCC received either TARE or one of the two other embolization treatments. Patients remained in a "watch and wait" state for tumor downstaging that allowed them to move to health states such as liver transplant, resection, systemic therapies, or cure. Clinical input parameters were retrieved from the published literature, and where values could not be sourced, assumptions were made and validated by clinical experts. Health benefits were quantified using quality-adjusted life years (QALYs). Cost input parameters were obtained from various sources, including the Medicare Cost Report, IBM® Micromedex RED BOOK, and published literature. At five years, TARE was found to be cost-saving (saving $15,779 per person compared to cTACE) and produced 0.33 more QALYs per person than cTACE. TARE cost $13,696 more but produced 0.33 more QALYs than DEE-TACE, with an incremental cost-effectiveness ratio of $41,474 per QALY gained at five years. After accounting for parameter uncertainty, the likelihood of TARE being cost-effective was at least 90% against all comparators at a cost-effectiveness threshold of $100,000 per QALY gained. TARE produces more QALYs than cTACE and DEE-TACE, with a high probability of being cost-effective against both comparators. The Barcelona Clinic Liver Cancer guideline recommends the use of transarterial radioembolization (TARE), conventional (cTACE), or drug-eluting bead transarterial chemoembolization (DEE-TACE) for treating hepatocellular carcinoma (HCC). This study evaluated the cost-effectiveness of TARE versus two alternative embolization treatments (cTACE and DEE-TACE) in treating patients with unresectable early- to intermediate-stage HCC. A cohort-based Markov model was developed to analyze the costs and benefits of these treatments from a US healthcare perspective within a 5-year time horizon. A 20-year time horizon was assessed as a scenario. In the model, patients were assigned to receive TARE, cTACE, or DEE-TACE and remained in the "watch and wait" stage for tumor downstaging. Data used in the model was taken from previous studies and in consultation with clinical experts. The benefits of the treatments were measured by considering the impact on the patient's quality of life. The costs associated with the treatments were obtained from various sources, including reports, publicly available databases, and published literature. The findings show that TARE is not only cost-saving compared to cTACE but also results in a higher number of quality-adjusted life years (QALYs) per person. While TARE was more expensive than DEE-TACE, it produced more QALYs, further indicating more favorable patient outcomes and overall treatment effectiveness. These findings could potentially impact resource allocation and decision-making for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Apixaban and rivaroxaban are two direct-acting oral anticoagulants (DOACs) recommended for thromboprophylaxis in cancer patients treated with chemotherapy in an ambulatory setting. We aimed to assess the cost-utility of thromboprophylaxis with apixaban and rivaroxaban vs no thromboprophylaxis in ambulatory cancer patients starting chemotherapy with an intermediate-to-high risk of venous thromboembolism (VTE), Khorana score ≥ 2 points. A cost-effectiveness analysis was performed from the perspective of Spain's National Health System (NHS) using an analytical decision model in the short-term (180 days) and a Markov model in the long-term (5 years). Transition probabilities were obtained from randomized, double-blind, placebo-controlled clinical trials of apixaban and rivaroxaban in adult ambulatory patients with cancer at risk for VTE, treated with chemotherapy (AVERT and CASSINI trials). The costs (€2,021) were taken from Spanish sources. The utilities of the model were obtained through the EQ-5D questionnaire. Deterministic (base case) and probabilistic (second-order Monte Carlo simulation) analyses were conducted. In the probabilistic sensitivity analysis, apixaban generated a cost per patient of €1,082 ± 187, with a 95% confidence interval (CI) of €713–1,442, while no prophylaxis produced a cost per patient of €1,146 ± 218, with a 95% CI of €700–1,491, with a saving of €64 per patient and a gain of 0.008 QALYs. Likewise, rivaroxaban provided a cost per patient of €993 ± 133, with a 95% CI of €748–1,310, while no prophylaxis produced a cost per patient of €872 ± 152, with a 95% CI of €602–1,250, with an additional expense of €121 per patient and a gain of 0.008 QALYs. In thromboprophylaxis of cancer patients, the use of apixaban and rivaroxaban generated similar costs compared to non-prophylaxis, without the difference found being statistically significant, with a clinically insignificant QALY gain. [ABSTRACT FROM AUTHOR]

Chemotherapy drugs have been used for a long time in the treatment of cancer, but serious side effects are caused by the inability of the drug to be solely delivered to the tumor when treating cancer with chemotherapy. Natural products have attracted more and more attention due to the antitumor effect in multiple ways, abundant resources and less side effects. Therefore, the combination of natural active ingredients and chemotherapy drugs may be an effective antitumor strategy, which can inhibit the growth of tumor and multidrug resistance, reduce side effects of chemotherapy drugs. Nano-drug co-delivery system (NDCDS) can play an important role in the combination of natural active ingredients and chemotherapy drugs. This review provides a comprehensive summary of the research status and application prospect of nano-delivery strategies for the combination of natural active ingredients and chemotherapy drugs, aiming to provide a basis for the development of anti-tumor drugs. [ABSTRACT FROM AUTHOR]

The systemic drug has historically been preferred for the treatment of the majority of pathological conditions, particularly liver cancer. Indeed, this mode of treatment is associated with adverse reactions, toxicity, off-target accumulation, and rapid hepatic and renal clearance. Numerous efforts have been made to design systemic therapeutic carriers to improve retention while decreasing side effects and clearance. Following systemic medication, local administration of therapeutic agents allows for higher 'effective' doses with fewer side effects, kidney accumulation, and clearance. Hydrogels are highly biocompatible and can be used for both imaging and therapy. Hydrogel-based drug delivery approach has fewer side effects than traditional chemotherapy and can deliver drugs to tumors for a longer time. The chemical and physical flexibility of hydrogels can be used to achieve disease-induced in situ accumulation as well as subsequent drug release and hydrogel-programmed degradation. Moreover, they can act as a biocompatible depot for localized chemotherapy when stimuli-responsive carriers are administrated. Herein, we summarize the design strategies of various hydrogels used for localized chemotherapy of liver cancer and their delivery routes, as well as recent research on smart hydrogels. [ABSTRACT FROM AUTHOR]

To explore the essential meaning of how sensory disturbances caused by Oxaliplatin influence self-understanding and freedom to live an everyday life among survivors after colorectal cancer. Data was generated by means of a semi-structured individual interview with eight survivors after colorectal cancer who continued to experience chemotherapy-induced peripheral neuropathy at least one year after completing chemotherapy with Oxaliplatin. Data analysis was guided by existential phenomenology and descriptive life-world research. The essential meaning was structured by four constituents. 1) An unpleasant fluctuating sensation which is impossible to ignore, 2) Breaking through of noise and pain despite struggling to keep them at bay, 3) Continuously feeling ill despite being cured, and 4) Bodily constraints that impact self-understanding and limit enjoyment of life. The survivors used distraction to keep the sensory disturbances at bay but were forced to adapt to a new self-understanding as sufferers after chemotherapy despite being cured of their cancer disease. This way of being-in-the-world was understood by survivors, their families and healthcare professionals as a necessary price to pay to be alive. However, marked as sufferer after chemotherapy, the participants' everyday style of experience and life revealed as an ill health condition, which limited their ability to accomplish everyday activities as before and their freedom to realize their potential—the "I can". [ABSTRACT FROM AUTHOR]

A common chemotherapy regimen in post-transplant lymphoproliferative disease (PTLD) following solid organ transplants (SOT) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). This study reviews the quantitative evidence for long-term consequences associated with components of CHOP identified from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cited references were screened using prespecified criteria (English, systematic review, randomized controlled trial n > 100, observation study n > 100, case series n > 20). Relevant data were extracted and synthesized. Of 61 studies, 66% were retrospective cohort studies, 28% were in the US, and 95% enrolled pediatric patients. No study focused specifically on the CHOP regimen. Long-term consequences for CHOP components observed in >3 studies included cardiac toxicity (n = 14), hormone deficiencies/infertility (n = 14), secondary leukemia (n = 7), osteonecrosis (n = 6), and bladder cancer (n = 4). These effects are significant, impact a high percentage of patients, and occur as early as one year after treatment. Although none of the studies focused specifically on the CHOP regimen, 30%, 23%, and 15% evaluated alkylating agents (e.g. cyclophosphamide), anthracyclines (e.g. doxorubicin), and corticosteroids (e.g. prednisone), respectively. All three product classes had a dose-dependent risk of long-term consequences with up to 13.2-fold, 27-fold, 16-fold, 14.5-fold, and 6.2-fold increase in risk of heart failure, early menopause, secondary leukemia, bladder cancer, and osteonecrosis, respectively. Lymphoma patients had significantly elevated risks of cardiac toxicity (up to 12.2-fold), ovarian failure (up to 3.8‐fold), and osteonecrosis (up to 6.7-fold). No studies were found in PTLD or SOT. Safe and effective PTLD treatments that potentially avoid these long-term consequences are urgently needed. [ABSTRACT FROM AUTHOR]

Inflammation of actinic keratoses (AK) was originally described with systemic 5-fluorouracil, and led to the development of topical fluorouracil. Similar observations using different chemotherapeutics may point to other drugs with a potential for repositioning. This systematic review aims to evaluate chemotherapeutic agents linked to inflammation-induced cure of AK. This systematic review was registered in PROSPERO (CRD42022346168) and followed PRISMA guidelines. A comprehensive literature search for eligible original articles written in English and published in peer-reviewed journals until July 13, 2022 was conducted in MEDLINE and Embase. 28 articles met inclusion criteria accounting for 36 patients (mean age 68.4 ± 8.3 years) with inflamed AK, exposed to 21 different chemotherapeutic agents – 21/36 (58.3%) received monotherapy and 15/36 (41.7%) received multidrug combinations. Regression was complete in 13/28 (46.4%) and partial in 14/28 (50.0%) of inflamed AK. Cure rates of inflamed AK in multidrug combinations were not superior to monotherapies (p =.252), leading to the observation that the majority of the former (14/15; 93.3%) encompassed one of five chemotherapeutic agents linked to AK inflammation also as a monotherapy. Overall, inflammation partially/completely cured AK in 96.4% of patients (27/28). Taxanes, pemetrexed, and doxorubicin might have the potential for the management of AK. [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]

Immune checkpoint inhibitors (ICI) have not yielded significant efficacy in pancreatic ductal adenocarcinoma (PDA), despite the role of the innate and adaptive immune systems on progression and survival. However, recently identified pathways have identified new targets and generated promising clinical investigations into promoting an effective immune-mediated antitumor response in PDA. We review biological mechanisms associated with immunotherapy resistance and outline strategies for therapeutic combinations with established and novel therapies in PDA. Pancreatic cancers rarely benefit from treatment with ICI due to an immunosuppressive tumor microenvironment (TME). New understandings of factors associated with the suppressive TME include low- and poor-quality neoantigens, constrained effector T cells infiltration, and the presence of a dense, suppressive myeloid cell population. These findings have been translated into new clinical investigations evaluating novel therapies in combination with ICI and/or standard systemic chemotherapy and radiotherapy. The epithelial, immune, and stromal compartments are intricately related in PDA, and the framework for successful targeting of this disease requires a comprehensive and personalized approach. [ABSTRACT FROM AUTHOR]

Antineoplastic treatments can negatively affect body composition, leading to metabolic derangements and worse clinical outcomes in breast cancer patients. This scoping review assesses body adiposity changes during breast cancer therapy. We included clinical and observational studies, published until the last search date in any language, with women aged >18 years, after breast cancer diagnosis, at any clinical stage and with any history of breast cancer treatment, who had body adiposity quantified by imaging tools at least twice during follow-up. In total, 17 studies were included (n = 1,009 individuals), six of which found a significant increase in body adiposity during treatment, two found a significant decrease, one presented divergent findings according to the imaging method and the analyzed body adiposity depots, and eight studies found no significant change in the outcome. Selective estrogen receptor modulators were associated with increased body adiposity, whereas aromatase inhibitors were associated with its decrease (n = 3). Chemotherapy was associated with increased body adiposity (n = 1), and monoclonal antibody with reduced brown adipose tissue activity (n = 1). Breast cancer treatment may have different effects on body adiposity, according to its mechanisms and protocols. Further studies are necessary to better elucidate this scenario. [ABSTRACT FROM AUTHOR]

Sarcopenia, defined as low-skeletal muscle mass (LSMM), can be assessed by imaging modalities. Our aim was to establish the effect of LSMM on overall survival (OS) and progression-free survival (PFS) in gastric cancer patients undergoing palliative chemotherapy based on a large patient sample. MEDLINE library, Cochrane and SCOPUS databases were screened for the associations between LSMM and mortality in advanced gastric cancer patients. The primary endpoint of the systematic review was the hazard ratio of LSMM on OS and PFS. In total, seven studies were suitable for the analysis and included into the present study. The included studies comprised 668 patients with advanced gastric cancer. The identified frequency of LSMM was 48.05%. The pooled hazard ratio for the effect of LSMM on OS was 1.31 [95% CI 0.96–1.77], p = 0.08, in univariate analysis and 1.21 [95% CI 0.94–1.56], p = 0.13, in multivariate analysis. For PFS, the pooled hazard ratio for the effect of LSMM on PFS was 1.76 [95% CI 0.66–4.66], p = 0.26. LSMM did not significantly affect OS and PFS in patients with advanced gastric cancer undergoing palliative chemotherapy. Further research is needed to elucidate possible influences of LSMM on survival in this tumor entity. [ABSTRACT FROM AUTHOR]

The use of (Netupitant and Palonosetron) combination to treat nausea and vomiting in cancer chemotherapy patients has been authorized by the Food and Drug Administration. For the simultaneous determination of Netupitant (NET) and palonosetron (PAL) in the presence of two of their related substances and in their dosage form, a sensitive and selective RP-HPLC method has been developed and validated. The aforementioned medications were separated and quantified with the help of experimental design. The Box-Behnken design was used in the experiment to optimize the chromatographic method's analytical parameters. It employed RP-HPLC with a UV detector. Waters ODS-C18 column (3.5 µm, 75 × 4.6 mm) with a mobile phase composed of acetonitrile: 25 mM phosphate buffer (pH = 3.5) in a gradient mode at 254 nm was employed to separate the cited drugs and their impurities. Palonosetron was linear over the concentration range (1–50 µg/mL) and Netupitant (10–100 µg/mL). According to ICH guidelines, the new method underwent thorough validation. Between the proposed method's results and those from the reported method, there was no significant difference. It is easy to apply the technique to the analysis of the specified drugs in their combination dosage form for quality control considerations. [ABSTRACT FROM AUTHOR]

The proportion of cancer patients that survive is increasing because of improvements in cancer therapy. However, some cancer treatments, such as chemo- and radio-therapies, can cause considerable damage to reproductive function. The issue of fertility is paramount for women of childbearing age once they are cured from cancer. For those patients with prepubertal or haematogenous cancer, the possibilities of conventional fertility treatments, such as oocyte or embryo cryopreservation and transplantation, are limited. Moreover, ovarian tissue cryopreservation as an alternative to fertility preservation has limitations, with a risk of re-implanting malignant cells in patients who have recovered from potentially fatal malignant disease. One possible way to restore fertility in these patients is to mimic artificially the function of the natural organ, the ovary, by grafting isolated follicles embedded in a biological scaffold to their native environment. Construction and cryopreservation of an artificial ovary might offer a safer alternative option to restore fertility for those who cannot benefit from traditional fertility preservation techniques. This review considers the protocols for constructing an artificial ovary, summarises advances in the field with potential clinical application, and discusses future trends for cryopreservation of these artificial constructions. [ABSTRACT FROM AUTHOR]

To investigate the role of combined systemic and local chemotherapy in improving the survival of patients with vitreoretinal lymphoma (VRL). Patients with VRL consecutively seen from 2006 to 2020 were retrospectively reviewed; data on the presence and time of central nervous system (CNS) involvement and treatment regimen (systemic, local or combined chemotherapy) were collected. Overall survival (OS) and progression-free survival (PFS) were calculated for each group. Forty-three eyes of 22 subjects with histology-proven VRL were included. Mean time of survival was 64.8 months (SE±10.8). Twelve patients (57%) presented CNS involvement, which was significantly associated with progression (r = 0.48, P =.03) and death (r = 0.56, P =.009). The isolated primary VRL group had a 5-year OS of 80%. Combined systemic and local chemotherapy reduced the risk of death by 82% (hazard ratio 0.18[0.04– 0.85]) in the entire cohort. Combined systemic and local chemotherapy significantly improved OS but not PFS of patients affected by VRL. [ABSTRACT FROM AUTHOR]

Malnutrition among colorectal cancer patients can impair quality of life and decrease survival. This study evaluated the nutritional status of colorectal cancer patients and its association with quality of life among Filipino colorectal cancer patients seen in a tertiary hospital. A cross-sectional study was conducted among colorectal cancer patients seen at the Philippine General Hospital between December 1, 2019 and February 28, 2020. Nutritional status was evaluated using the Subjective Global Assessment, while quality of life was assessed using the EORTC QLQ-C30. Descriptive statistics, ANOVA and logistic regression were employed for analysis. Among 292 patients, malnutrition was noted in 76.4%. Stage III cancer had a higher odds for malnutrition (OR (odds ratio) = 6.22, 95% confidence interval (CI): 1.59, 24.42). Patients who received or were currently receiving chemotherapy were less likely to develop malnutrition (OR = 0.35, 95% CI: 0.18–0.69). Global health status and all functional subscale scores for the severely malnourished group were lower while the scores for symptom scales increased with the degree of malnutrition. There was a high prevalence of malnutrition among colorectal cancer patients and this was associated with poor quality of life. Future directions emphasizing early nutritional screening and assessment are recommended. [ABSTRACT FROM AUTHOR]

The aims of this study were to assess the presence of dysgeusia in patients receiving anticancer therapy and to explore possible factors influencing its occurrence. A total of 242 adult patients with histological diagnoses of malignant neoplasia and undergoing all types of anticancer treatment were included in the analysis. Data were collected from May 2019 to November 2019 at the Unit of Medical Oncology of Careggi University Hospital, Florence, Italy. Dysgeusia was assessed using the Chemotherapy-induced Taste Alteration Scale (CiTAS), while treatment-related symptoms were assessed using the Common Terminology Criteria for Adverse Events (CTCAE). Patients were aged 68 ± 13 years, mostly males (65%). A large proportion of them was undergoing chemotherapy (42.2%), while the others were receiving immunotherapy (20.7%), hormone therapy (15.5%), targeted therapy (12.8%), or a combination of them. Overall, 21.5% of patients reported dysgeusia, 17.4% nausea, 10.7% dysosmia, 9.9% xerostomia, 4.5% mucositis, and only 3.7% vomiting. The targeted therapy showed the greatest adverse effects, followed by chemotherapy, immunotherapy, and hormone therapy. When patients with dysgeusia were analyzed, phantogeusia and parageusia was the most affected dimension of gustatory disorders. Significant differences (p < 0.05) in CiTAS scores were found according to treatment-related symptoms for nausea and mucositis. [ABSTRACT FROM AUTHOR]

There is no consensus on the optimal palliative first-line chemotherapy regimen for East Asian patients with advanced esophageal squamous cell carcinoma (ESCC). We conducted a systematic review using a literature search of PubMed, Embase, and the Cochrane Library without date restrictions, and abstracts from major oncology congresses. Studies meeting the following criteria were included: East Asian patients ≥18 years old with metastatic/locally advanced unresectable ESCC; first-line chemotherapy; reporting of overall survival, progression-free survival, duration of response, overall response rate, and/or safety; randomized controlled trials, non-randomized controlled trials, and prospective or retrospective comparative studies. In total, 39 articles were identified for: platinum plus fluoropyrimidine (n = 9), platinum plus taxane (n = 16), platinum plus fluoropyrimidine plus taxane (n = 7), platinum plus fluoropyrimidine plus other (n = 3), irinotecan plus platinum (n = 2), taxane plus fluoropyrimidine (n = 1). The available data supports both taxane plus platinum regimens and fluoropyrimidine plus platinum regimens in the first-line treatment of East Asian patients with ESCC. Compared with data from doublet chemotherapy studies, triplet chemotherapy appeared to improve ORR, but did not seem to prolong OS, possibly due to an increased incidence of adverse events. [ABSTRACT FROM AUTHOR]

Heterocyclic nucleus is vital in medicinal chemistry and has allured significant attention in chemotherapeutic domain. Oxadiazole, a five-membered nitrogen–oxygen-containing heterocyclic core has remarkable anticancer activity. Mechanism associated in defeating tumor corresponds with inhibiting various enzymes and growth factors. Considering the importance of oxadiazole and its derivatives in this panic issue worldwide, this review has discussed research carried out from last 7 years and also their future outlook in drug development as antineoplastic agents. The objective of this review is to emphasize on anticancer activity of 1,3,4-oxadiazole and 1,2,4-oxadiazole derivatives. The precised features and framework of each research topic is introduced for helping the readers in understanding the perspective of the context in better way. [ABSTRACT FROM AUTHOR]

Cancer chemotherapy and radiotherapy may result in mucositis characterized by stem cell damage and inflammation in the gastrointestinal tract. The molecular mechanisms underlying this pathology remain unknown. Based on the assumption that mitochondrial CPG-DNA (mtDNA) released and sensed by TLR9 could underlie mucositis pathology, we analyzed the mtDNA levels in sera as well as inflammatory and disease parameters in the small intestine from wild-type (WT) and TLR9-deficient mice (TLR9−/−) in an experimental model of intestinal mucositis induced by irinotecan. Additionally, we verified the ability of WT and TLR9−/− macrophages to respond to CpG-DNA in vitro. WT mice injected with irinotecan presented a progressive increase in mtDNA in the serum along with increased hematocrit, shortening of small intestine length, reduction of intestinal villus:crypt ratio and increased influx of neutrophils, which were followed by higher expression of Nlrp3 and Casp1 mRNA and increased IL-1β levels in the ileum when compared to vehicle-injected mice. TLR9-deficient mice were protected in all these parameters when compared to WT mice. Furthermore, TLR9 was required for the production of IL-1β and NO after macrophage stimulation with CpG-DNA. Overall, our findings show that the amount of circulating free CpG-DNA is increased upon chemotherapy and that TLR9 activation is important for NLRP3 inflammasome transcription and further IL-1β release, playing a central role in the development of irinotecan-induced intestinal mucositis. We suggest that TLR9 antagonism may be a new therapeutic strategy for limiting irinotecan-induced intestinal inflammation. [ABSTRACT FROM AUTHOR]

Malnutrition can affect the patient diagnosed with, and treated for, cancer. However, until a dedicated study is completed, estimates of malnutrition rates will be disparate and unrepresentative of cancer patients' nutritional reality. Objective: To estimate the prevalence of malnutrition among patients being cared for cancer in Latin American (LATAM) hospitals by means of a multicenter, multinational study. Methods: The Latin American Study of Malnutrition in Oncology (LASOMO) was completed with 1,842 patients (Women: 56.2%; Age ≥ 60 years: 43.2%; Chemotherapy: 55.1%; Radiotherapy: 17.8%; Surgery: 27.1%) assisted at 52 health centers from 10 LATAM countries. Malnutrition prevalence was estimated from the (B + C) scores assigned to the patient with the Subjective Global Assessment by Detsky et al. (1987). Malnutrition prevalence was distributed regarding the demographic features of the patient, the primary tumor location, and the current cytoreducing treatment. Results: Malnutrition affected 59.1% of the surveyed patients. Malnutrition prevalence was higher among male patients and those with tumors of the digestive tract and the hemolymphopoietic system. Malnutrition was also associated with the current cytoreducing modality, with chemotherapy returning the highest prevalence. Conclusions: Malnutrition can be present in more than half of the patients being cared for cancer in LATAM health centers. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.2014902 [ABSTRACT FROM AUTHOR]

It has been known for close to 100 years that the metabolism of cancer cells is altered and different than that of healthy cells in the body. On that basis, we have developed an entirely novel approach to managing cancer, termed Targeted Nutrients Deprivation (TND). TND employs a formulated diet depleted of multiple non-essential amino acids (NEAAs) that are required by tumor cells but not by normal cells. Cancer cells specifically require those NEAAs due to their heightened and rewired metabolism. We demonstrated that our first proprietary formulated TND diet—FTN203—significantly reduced the growth of multiple human tumor xenografts in mouse. In combination with chemotherapy and immunotherapy, FTN203 further enhanced therapeutic efficacy. Reliance on FTN203 as the sole nutrition source was shown to be safe without causing detrimental body-weight loss or internal organ damage. Our findings indicate that TND is a novel and safe approach to managing cancer. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.2013904. [ABSTRACT FROM AUTHOR]

Chemotherapy is an aggressive form of treatment for cancer and its toxicity directly affects the eating behavior of many patients, usually by adversely affecting their sense of smell and/or taste. These sensory alterations often lead to serious nutritional deficiencies that can jeopardize the patient's recovery, and even continue to affect their lives once treatment has terminated. Importantly, however, not all patients suffer from such alterations to their chemical senses; and those who do, do not necessarily describe the side effects in quite the same way, nor suffer from them with equal intensity. The origin of these individual differences between cancer patients undergoing chemotherapy treatment has not, as yet, been studied in detail. This review is therefore designed to encourage future research that can help to address the perceptual/sensory problems (and the consequent malnutrition) identified amongst this group of patients in a more customized/personalized manner. In particular, by providing an overview of the possible causes of these large individual differences that have been reported in the literature. For this reason, in addition to the narrative bibliographic review, several possible strategies that could help to improve the chemosensory perception of food are proposed. [ABSTRACT FROM AUTHOR]

Hematological neoplasias are the fourth cause of death in the world. All of them are responsible of bad quality of life, due to heavy therapies administration and a lot of side effects correlated to. It arises a new concept of "multitherapy", in which fatty acids availment is used to contrast and reduce toxic effects and ameliorate chemotherapeutic agents asset. In Vitro studies have confirmed that fatty acids, in particular ω-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are able to help canonical therapies to contrast cancer cell expansion and proliferation. In clinical trials it is also almost clear that fatty acids are useful to build new personalized therapies for a better condition of life. In this review we have summarized most recent studies on cancer cell lines and clinical trials on patients with fatty acids supplementation in diet therapies. We have found that fatty acids could be useful to contrast side effects during chemotherapeutic drugs therapies; they are also able to block cancer cell metabolic pathways for proliferation and contrast adverse effects, even when they are used in combination with traditional therapies or innovative, like monoclonal antibodies or CAR-T therapy. These aspects are crucial for better health condition of patients. [ABSTRACT FROM AUTHOR]

The selectivity of chemotherapeutic agents for liver cancer is poor. When they kill tumour cells, they produce serious adverse reactions in the whole body and multidrug resistance (MDR) is also a major hurdle in liver cancer chemotherapy. Combination therapy is a useful method for overcoming MDR and reducing toxic and side effects. In this study, we developed a long-circulating codelivery system, in which doxorubicin (DOX) and schizandrin A (SchA) are combined against MCF-7/ADR cells. The DOX-SchA long-circulating liposome (DOX-SchA-Lip) was prepared using ammonium sulphate gradient method. The two drugs were co-encapsulated into the distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-mPEG2000) liposome and the liposome had an average particle size of (100 ± 3.5) nm and zeta electrical potential of (–31.3 ± 0.5) mV. The average encapsulation rate of DOX was 97.98% and that of SchA was 86.94%. DOX in liposome had good sustained-release effect. The results showed that DOX-SchA-Lip could significantly prolong the half-life (t1/2z) of the DOX and SchA, increase their circulation time in vivo, improve its bioavailability and reduce their side effects. Liposome can effectively induce early apoptosis of HepG2/ADR cells and the cell cycle was blocked in S-phase by DOX-SchA-Lip in a dose-dependent manner. The IC50 of compound liposome to HepG2 and HepG2/ADR were 0.55 μmol/L and 1.38 μmol/L, respectively, which could significantly reverse the resistance of HepG2/ADR and the reversion multiple was 30.28. It was verified that DOX-SchA-Lip can effectively kill tumour cells and reverse MDR. [ABSTRACT FROM AUTHOR]