Number Of Chemotherapeutic Agents Research Articles

The prevalence and predictors of herb-drug interactions among Iranian cancer patients during chemotherapy courses

BackgroundThe concurrent usage of herbal medicines with conventional therapies is an important concern in cancer treatment which can lead to unexpected consequences like herb-drug interactions. This study aimed to determine the prevalence of potential herb-drug interactions and to predict factors associated with herb-drug interactions for cancer patients.MethodsThis cross-sectional study was conducted among a convenience sample of 315 cancer patients referring to the oncology clinics of Kerman city in 2018. Data were collected via comprehensive face-to-face interviews and medical chart reviews. A drug interaction checker was used to determine herb-drug interactions. The information of patients was compared based on herb-drug interactions using bivariable logistic regression models, and predictors were determined by the multivariable logistic regression model. All analyses were performed by Stata software version 16.ResultsOf 262 patients (83.2% of the patients) who used herbal medicines, 209 patients [79.8% (95% Confidence Intervals (CI): 75.2 – 85.1)] had potential herb-drug interactions. Chamomile was the most popular herbal medicine (n = 163, 78.0%), and minor and moderate herb-drug interactions were caused by green tea (n = 34, 16.3%) and peppermint (n = 78, 37.5%). The number of chemotherapeutic agents (OR: 1.92, 95% CI: 1.43–2.58; P-value < 0.0001) and the experienced of pain during chemotherapy courses (OR = 2.22, 95%CI:1.00–4.94; P-value = 0.04) were some of the predictors of herb-drug interactions among cancer patients.ConclusionHerbal medicine use during chemotherapy was found prevalent among cancer patients; of them, the experience of potential herb-drug interactions was highly frequent. Oncologists and clinical pharmacologists are recommended to take into account challenges associated with herb-drug interactions in their routine practices, particularly during chemotherapy among these patients.

Vitamin D Relation to Busulphan in Pediatrics Undergoing Hematopoietic Stem Cell Transplantation

Vitamin D is an essential compound that plays an important role in biological activities. There are two main sources of vitamin D: either through the conversion of 7-dehydrocholesterol in the skin by UVB light or through absorption in the small intestine via food intake or dietary supplements. Vitamin D from both sources undergoes a first hydroxylation in the liver through cytochrome P 450 forming 25 (OH) vitamin D, followed by a second hydroxylation that takes place in the kidneys resulting in the active form of the vitamin D (1.25 (OH)2 Vitamin D). Busulphan is an alkylating agent used mainly as part of the myeloablative conditioning prior to hematopoietic stem cell transplantation (HSCT). Recent studies have shown that vitamin D can have some interaction (additive, synergistic, or antagonistic) with a number of chemotherapeutic agents; therefore, we have investigated the relation between vitamin D and busulphan.In the present investigation, the relation between vitamin D and busulphan was evaluated in 44 pediatric patients undergoing stem cell transplantation. The patients received busulphan (1.8-2mg/kg twice a day for four days) as a prat of their condition regimen prior to HSCT. Patients were divided into two groups; the first group received the drug orally (n=20) while the second was treated intravenously (n=24). Blood samples were collected from these patients, and busulphan was quantified in the plasma using gas chromatography with electron capture detector, while 25 (OH) Vitamin D levels were measured using ELISA.Our results showed that the levels of vitamin D before the start of the conditioning were positively correlated with the first busulphan AUC in the group of patients receiving the drug orally (R2=0.25, P<0.05). Moreover, a significant (p<0.0001) increase was observed in the plasma levels of vitamin D (290 -1190 ng/mL) at 24h after the start of busulphan conditioning compared to that found before the start of busulphan treatment (15-162 ng/mL).On the other hand, no significant changes in the vitamin D levels were observed in the patients receiving busulphan intravenously. To confirm the previous findings, two groups of mice were treated with busulphan (25mg/Kg/day) dissolved in 5% DMSO either orally (PO) or intraperitoneally (IP) once daily for 4 days. Mice were fed with standard chew (Teklad Global 18% Protein Rodent Diet containing vitamin D3 at a concentration of 1.5 IU/g) and food intake was monitored daily. Two control groups (received oral 5% DMSO or intraperitoneal 5% DMSO and negative controls) were run in parallel. Vitamin D levels were measured in mice plasma using ELISA. The results showed that vitamin D levels were higher in mice treated with oral busulphan compared to those who received the drug via IP administration.In conclusion, the present results indicate that vitamin D levels before conditioning may influence busulphan AUC when the drug is administered orally and hence the clinical outcome. On the other hand, the oral administration of busulphan has a significant effect on the vitamin D levels, which suggest that the observed effects are mainly based on alteration in vitamin D uptake. Currently, further studies are ongoing to investigate the underlying mechanisms. Altogether, suggest that busulfan levels and vitamin D intake should be monitored in patients treated with oral busulphan in order to avoid their toxicities and improve the clinical outcome. DisclosuresNo relevant conflicts of interest to declare.

Comparative proteomic analysis of SLC13A5 knockdown reveals elevated ketogenesis and enhanced cellular toxic response to chemotherapeutic agents in HepG2 cells

Solute carrier family 13 member 5 (SLC13A5) is an uptake transporter mainly expressed in the liver and transports citrate from blood circulation into hepatocytes. Accumulating evidence suggests that SLC13A5 is involved in hepatic lipogenesis, cell proliferation, epilepsy, and bone development in mammals. However, the molecular mechanisms behind SLC13A5-mediated physiological/pathophysiological changes are largely unknown. In this regard, we conducted a differential proteome analysis in HepG2 and SLC13A5-knockdown (KD) HepG2 cells. A total of 3826 proteins were quantified and 330 proteins showed significant alterations (fold change ≥1.5; p < .05) in the knockdown cells. Gene ontology enrichment analysis reveals that 38 biological processes were significantly changed, with ketone body biosynthetic process showing the most significant upregulation following SLC13A5-KD. Catalytic activity and binding activity were the top two molecular functions associated with differentially expressed proteins, while HMG-CoA lyase activity showed the highest fold enrichment. Further ingenuity pathway analysis predicted 40 canonical pathways and 28 upstream regulators (p < .01), of which most were associated with metabolism, cell proliferation, and stress response. In line with these findings, functional validation demonstrated increased levels of two key ketone bodies, acetoacetate and β-hydroxybutyrate, in the SLC13A5-KD cells. Additional experiments showed that SLC13A5-KD sensitizes HepG2 cells to cellular stress caused by a number of chemotherapeutic agents. Together, our findings demonstrate that knockdown of SLC13A5 promotes hepatic ketogenesis and enhances cellular stress response in HepG2 cells, suggesting a potential role of this transporter in metabolic disorders and liver cancer.

A retrospective analysis of cost and survival outcomes based on consolidation regimens in primary central nervous system lymphoma.

e14544 Background: Treatment for Primary Central Nervous System Lymphoma (PCNSL) includes induction therapy consisting of polychemotherapy including high-dose methotrexate followed by consolidation therapy. There are various induction and consolidation regimens with wide variability in their treatment duration, inpatient vs outpatient administration, and the number of chemotherapeutic agents utilized. We performed a comparative cost and efficacy analysis of three consolidation techniques in an effort to provide insight into the cost-benefit of these treatment regimens. Methods: Patients treated for newly diagnosed PCNSL at our institution after July 1, 2012 were retrospectively reviewed. Patients who completed one of the following regimens and received consolidation therapy at our institution were included: rituximab/methotrexate/vincristine/procarbazine (R-MVP), rituximab/methotrexate/temozolomide (R-MT), or rituximab/methotrexate (R-M) for induction followed by consolidation with etoposide/cytarabine (EA), high-dose cytarabine (HIDAC), or high-dose chemotherapy with autologous stem cell rescue (HDC-ASCR). Cost to health system was derived from a Value Driven Outcomes tool and filtered to compare major costs of treatment. Survival was calculated from the date of diagnosis and last date of known survival. Results: Twenty-two patients met eligibility criteria and received the following four treatment regimens: R-MT+EA (12), R-MT+ HDC-ASCR (3), R-M+ HDC-ASCR (1), and R-MVP+HIDAC (6). Patients receiving HDC-ASCR (4) had a trend towards a more favorable overall survival (p = 0.0880) compared to the other two consolidation therapies with no recurrence or death in those patients treated with HDC-ASCR. Comparative cost analysis of facility and pharmacy costs of the three consolidation techniques found that HDC-ASCR was 40 times the cost of the cheapest treatment, HIDAC. Conclusions: This small retrospective review provides evidence that HDC-ASCR may be a superior consolidation strategy but with a profound increase in financial cost. To our knowledge this is the first study completed in the U.S. comparing treatment outcomes and cost in PCNSL. Based on our results, it is clear that a larger and prospective review could potentially shed light on selecting a standard of care based on cost-benefit analysis.

Hyponatremia in a Patient With Cancer

Hyponatremia in a Patient With Cancer

Thrombotic microangiopathy in cancer patients

Thrombotic microangiopathy (TMA) is a rare phenomenon, which is severe pathology based on systemic microvascular thrombosis. TMA is characterized by thrombocytopenia and signs of microangiopathic hemolytic anemia. The review presents a modern data on the pathogenesis of tumor-associated thrombotic microangiopathy, considers the interaction of various effectors related to both tumor growth and metastasis process ― immune system activation, endotheliopathy formation, use of chemotherapeutic agents and targeted therapy in the pathogenesis of various forms of TMA. The interaction between the tumor tissue, hemostasis and immune systems are of the type of cascade of mutual activation, thus leading to the formation of a vicious circle, resulting in damage to endothelium and thrombosis in the microcirculatory channel, that is, the development of TMA. The formation of thromboembolism, which includes tumor tissue in the microvessels of the lungs, contributes to the development of pulmonary tumor thrombotic microangiopathy (PTTM). Сancer patients have higher vWF levels and lower ADAMTS13 levels or/and activity than the general population, often also depending on the stage of cancer: vWF and ADAMTS13 have been shown to be associated with thrombotic complications in cancer patients, and ADAMTS13 shows prognostic potential. Increased expression of complement proteins and/or activation of complement during chemotherapy, infectious and inflammatory complications may also cause TMA development. Pathogenesis of thrombotic microangiopathy also is associated with numerous chemotherapeutic agents, such as mitomycin C, gemcitabine, cisplatin, carboplatin and Bevacizumab, an inhibitor of VEGF. This may be the result of both the direct toxic effect of the drug on endothelium and damage of it by immune complexes caused by expression of the VEGF-antibodies. Usage of number of chemotherapeutic agents, especially anti-VEGF and tyrosine kinase inhibitors, which have a direct toxic effect on endothelium, are associated with the development of TMA. Mechanisms causing the development of TMA are considered as components of the hemostasis system, leading to the development of chronic, long-lasting disorders of the hemostasis system (chronic DIC syndrome) and are associated with high incidence of thrombotic complications.

Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field.

Efficacy of palliative chemotherapy in elderly patients with colorectal cancer.

The number of old patients suffering from colorectal cancer rises. In clinical trials, old patients are underrepresented, and chemotherapy is significantly less often performed in elderly patients. We analyzed the impact of elder age for palliative chemotherapy in patients suffering from metastatic colorectal cancer, according to therapeutic drugs used, intensity of treatment performed, and therapeutic results. We analyzed consecutive patients with metastatic colorectal cancer treated in palliative intention in our department. Assessed data included age (</> 75years), sex, comorbidity, site of primary tumor, k-ras-status, site and amount of metastasis, number and kind ofchemotherapeutic agents used, number of consecutive therapy lines performed, dose intensity, toxicity, time between start and end of palliative chemotherapy, and overall survival. Prognostic variables were tested in uni- and multivariate analysis. Ninety-seven patients (69 < 75, 18 > 75 years) were included. Age groups were well balanced according to site of primary tumor, k-ras-mutational status, localization, and number of metastatic sites. Cardial and renal comorbidity was more frequent in elderly patients. The median number of chemotherapeutic drugs used and lines of therapy performed did not differ between age groups, except of oxaliplatin, which was significantly less often used in old patients. Median survival did not differ between age groups (23.4 vs. 23.5 months). In multivariate analysis, only left-sided primary tumor and more than 3lines of therapy performed were prognostic positive variables. Old patients can profit from palliative chemotherapy to the same extent as younger ones.

Cyclophosphamide-induced melanonychia in a patient with steroid dependent nephrotic syndrome: A rare presentation

Melanonychia is described as a brown to black pigmentation of nail, due to stimulation and hyperplasia of nail matrix. Various systemic disorders, trauma, inflammatory disorders, fungal infections, drugs, benign melanocytic hyperplasia, etc., are responsible for this condition, and most of them are benign. A number of chemotherapeutic agents can cause melanonychia. Cases of cyclophosphamide-induced melanonychia are not frequent. We report a 38-year-old female, a known case of steroid dependent nephrotic syndrome, who developed melanonychia on starting treatment with cyclophosphamide. It is a benign condition, which resolves on discontinuation of the drug.

Novel first-in-class small molecule targeting APE1/Ref-1 to prevent and treat chemotherapy-induced peripheral neuropathy (CIPN).

229 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is an acute and chronic debilitating side effect of a number of chemotherapeutic agents lacking FDA-approved interventions or strategies resulting in dose-limiting neurotoxicity. CIPN can persist following discontinuation of the drug with up to 40% of patients having continued CIPN five years after treatment ends. Thus, CIPN directly affects cancer survivorship, quality of life, and may limit future treatment options if cancer recurs. Although the cellular mechanisms mediating CIPN remain to be determined, several lines of evidence support the notion that DNA damage caused by anticancer therapies could contribute to the neuropathy. Methods: Using an experimental model of isolated sensory neurons in culture, we established a causal relationship between cancer-therapy-induced neurotoxicity and DNA damage and repair. Results: Genetically reducing the activity of APE1 increased the neurotoxicity produced by platin treatment, whereas augmenting the activity of APE1 lessened neurotoxicity. Furthermore, using a targeted small-molecule, APX3330, which increases DNA repair of APE1 in neurons, it lessened neurotoxicity using a variety of endpoints ex vivo; e.g. DNA damage, CGRP release. We will present data using animal models of CIPN demonstrating a protective effect of APX3330 using either cis- or oxaliplatin without diminishing the anti-tumor effect of the platins. A Phase 1 clinical trial for safety/RF2D for APX3330 has completed (NCT03375086). Conclusions: Effective prevention and management of CIPN hinges on understanding its pathophysiology. While multiple causal mechanisms may be at work, we believe that the induction of oxidative DNA damage in sensory neurons is a major cause of CIPN. Thus, enhancement of oxidative DNA damage repair by APX3330 results in reduction of CIPN.

Evaluating Nationwide Practice Patterns in Chemoradiotherapeutic Regimens and Relative Efficacy of Chemoradiation Versus Adjuvant Radiation for Grade III Gliomas

For newly diagnosed Grade III gliomas including anaplastic oligodendrogliomas (AO), anaplastic astrocytomas (AA) and anaplastic oligoastrocytomas (AOA), combined chemoradiotherapy (CRT) remains the current standard of care. Two landmark trials established multiagent (MA) chemoradiotherapy using PCV as first-line for 1p/19q-codeleted tumors. However, single-agent (SA) CRT using temozolomide is an alternative off-label option. Recently, interim analysis of CATNON confirmed that temozolomide-based SA-CRT offers significant survival benefit for 1p/19q-noncodeleted tumors. Here, we evaluated nationwide patterns in receipt of CRT and relative treatment efficacies for Grade III gliomas using the National Cancer Database (NCDB). Patients with a first primary diagnosis of AO, AA or mixed glioma treated from 2006-2014 were identified from the NCDB. WHO Grade III glioma patients were identified whose initial treatment courses involved surgery with or without adjuvant RT (55-63 Gy in 25-34 fractions) or CRT. Factors examined included facility type, location, age, sex, race, Charlson-Deyo score, median income, insurance and extent of resection (EoR). Overall survival was assessed by Kaplan-Meier and Cox proportional hazards modeling. Potential predictors of MA- vs SA-CRT were examined using multivariate logistic regression. Adjusted survival comparison was performed using propensity score matching. From a total of 21,877 AO, AA and mixed gliomas, 4,553 WHO Grade III glioma patients were identified that met inclusion criteria. Median age was 47. Most patients (72.5%) received combined chemoradiotherapy, while a minority received only adjuvant RT (8.1%). At a median follow-up of 4.6 years, median survival was 88.3, 59.1, and 32.5 months for patients treated with chemoradiation, adjuvant RT or surgery alone, respectively (p<0.001), which remained significant on 1- and 3-month landmark analyses. On multivariate analysis, factors associated with improved survival included EoR, adjuvant RT and receipt of chemotherapy along with AO or mixed glioma histology, younger age, non-Medicare status, lower Charlson-Deyo score and higher median income. Among 3200 patients who received chemoradiation using known number of chemotherapeutic agents, 3,088 (96.5%) received SA chemotherapy while only 112 (3.5%) received MA chemotherapy. Only EoR was associated with receipt of multi-agent chemotherapy (OR: 3.22 for STR vs. biopsy). Propensity score matched analysis detected no significant median survival difference between patients receiving SA vs. MA CRT (44.0 months vs. 53.6 months, p=0.36). Independent of WHO Grade III histology, chemoradiation was associated with improved survival. Interestingly, despite only recent randomized data confirming its efficacy, SA-CRT was much more frequently offered than MA-CRT nationwide. Further study is needed regarding relative efficacy, particularly for 1p/19q-codeleted tumors.

Are antineoplastic drug acute hypersensitive reactions a submerged or an emergent problem? Experience of the Medical Day Hospital of the Fondazione IRCCS Istituto Nazionale Tumori.

Acute hypersensitivity reactions are adverse events potentially associated with antineoplastic drug infusions. Their occurrence can be particularly relevant in an outpatient environment where time of administration and subsequent observation is limited to a short period of time. In addition, concern about the onset of more severe hypersensitivity reactions can limit subsequent use of crucial drugs. During a 3-year observational period, we collected a total of 240 infusional acute hypersensitivity reactions out of 56,120 administrations performed, with an overall incidence of 0.4%. In order of frequency, platinum derivatives, taxanes and monoclonal antibodies accounted for the highest incidences. Their relative frequency was: oxaliplatin, 2.5%; carboplatin, 0.4%; paclitaxel, 1.2%; docetaxel, 1.2%; trastuzumab, 1.2%, and rituximab, 1.2%. Since the number of chemotherapeutic agents is steadily increasing, much attention should be paid to such reactions, particularly when several administrations are performed daily, and where management of the potential risk associated with specific drugs is mandatory. Their occurrence represents an unpredictable, unexpected and often hard to manage contingency, and our opinion is that observation and consciousness of this issue are fundamental for its appropriate management. We describe our experience, emphasizing the role of this toxicity and explaining how this awareness allowed us to define some empirical rules to handle acute hypersensitivity reactions.

Pattern of Chemotherapy-Related Adverse Effects Among Adult Patients With Cancer Treated at Gondar University Referral Hospital, Ethiopia: A Cross-Sectional Study

Abstract 32 Purpose Adverse drug reactions (ADRs) are a global problem and constitute a major clinical problem in terms of human suffering. The high toxicity and narrow therapeutic index of chemotherapeutic agents makes oncology pharmacovigilance essential. The objective of the current study was to assess the pattern of ADRs that occur in patients with cancer who were treated with chemotherapy in a tertiary care teaching hospital in Ethiopia. Methods A cross-sectional study over a 2-year period from September 2013 to August 2015 was conducted in patients with cancer who underwent chemotherapy at Gondar University Referral Hospital Oncology Center. Data were collected directly from patients and their medical case files. Reported ADRs were assessed for causality using the WHO causality assessment scale and Naranjo’s algorithm. Severities of the reported reactions were also assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). Pearson’s χ2 test was used to examine the association between two categorical variables. Results A total of 815 ADRs were identified from 203 patients who were included in the study. The most commonly occurring ADRs were nausea and vomiting (18.9%), infections (16.7%), neutropenia (14.7%), fever and/or chills (11.3%), and anemia (9.3%). Platinum compounds (31.4%) were the most common group of drugs that caused ADRs. Of reported ADRs, 65.8% were grades 3 to 4 (severe level), 29.9% were grades 1 to 2 (mild level), and 4.3% were grade 5 (toxic level). Significant association was found between age, number of chemotherapeutic agents, and dose of chemotherapy with the occurrence of grades 3 to 5 toxicity. Conclusion The high incidence of chemotherapy-related ADRs among patients with cancer is of concern. Establishing an effective ADR monitoring and reporting system—oncopharmacovigilance—and creating awareness among health care professionals of the importance of ADR reporting may help prevent the problem. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST No COIs from the authors.

New tetrahydroisoquinoline-based P-glycoprotein modulators: decoration of the biphenyl core gives selective ligands.

P-glycoprotein (P-gp, MDR1) is a membrane transporter expressed in several regions of our body. It plays a crucial defense role as it mediates the efflux of hundreds of potentially toxic substances. However, P-gp is one of the main causes of failure in cancer chemotherapy, as a number of chemotherapeutic agents are P-gp substrates. Another interesting implication concerns the correlation between P-gp expression impairment and the onset of several central nervous system pathologies such as Alzheimer's and Parkinson's diseases. In view of these considerations, in the present study, a new series of P-gp modulators have been designed, synthesized and evaluated for their activity towards P-gp and two other sister proteins (BCRP and MRP1). The compounds, structurally correlated to the potent but non-selective P-gp inhibitor MC70 [4'-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-ylmethyl)biphenyl-4-ol], proved fairly selective towards P-gp, with a potency in the micromolar range. Compounds 5a, 5d and 12d proved capable of restoring doxorubicin toxicity in resistant cancer cells.

Perspectives in Head and Neck Medical Oncology.

The modern treatment of locoregionally advanced disease often requires a multimodality combination approach. A number of chemotherapeutic agents can be combined with radiation, but the platinum agent cisplatin, a potent radiation sensitizer, is best studied in head and neck cancer. Newer agents such as cetuximab can be used in combination with radiation therapy for those patients who cannot tolerate cisplatin. For chemotherapy-naïve patients with metastatic head and neck cancer who demonstrate a good performance status, platinum doublet regimens are commonly used. Doublet regimens generally improve response rates compared to single-agent chemotherapies, although they have not demonstrated a survival benefit over single agents and they have added toxicity. Immunotherapies, alternative cytotoxic chemotherapies, and targeted therapies are second-line options for patients with disease that has progressed on platinum-based therapy. Immunotherapy, in particular, has gained focus by enhancing the ability of the immune system to recognize and destroy malignant cells. When multimodal approaches are used, as in combined chemotherapy and radiation therapy, toxicities are increased. It is imperative that patients are followed closely in order to maximize treatment benefit while minimizing complications.

Pattern of chemotherapy-related adverse effects among adult cancer patients treated at Gondar University Referral Hospital, Ethiopia: a cross-sectional study.

BackgroundAdverse drug reactions (ADRs) are a global problem and constitute a major clinical problem in terms of human suffering. The high toxicity and narrow therapeutic index of chemotherapeutic agents makes oncology pharmacovigilance essential. The objective of the present study was to assess the pattern of ADRs occurring in cancer patients treated with chemotherapy in a tertiary care teaching hospital in Ethiopia.MethodsA cross-sectional study over a 2-year period from September 2013 to August 2015 was conducted on cancer patients undergoing chemotherapy at Gondar University Referral Hospital Oncology Center. Data were collected directly from patients and their medical case files. The reported ADRs were assessed for causality using the World Health Organization’s causality assessment scale and Naranjo’s algorithm. The severities of the reported reactions were also assessed using National Cancer Institute Common Terminology CTCAE version 4.0. The Pear-son’s chi-square test was employed to examine the association between two categorical variables.ResultsA total of 815 ADRs were identified per 203 patients included in the study. The most commonly occurring ADRs were nausea and vomiting (18.9%), infections (16.7%), neutropenia (14.7%), fever and/or chills (11.3%), and anemia (9.3%). Platinum compounds (31.4%) were the most common group of drugs causing ADRs. Of the reported ADRs, 65.8% were grades 3–4 (severe level), 29.9% were grades 1–2 (mild level), and 4.3% were grade 5 (toxic level). Significant association was found between age, number of chemotherapeutic agents, as well as dose of chemotherapy with the occurrence of grades 3–5 toxicity.ConclusionThe high incidence of chemotherapy-related ADRs among cancer patients is of concern. Setting up an effective ADR monitoring and reporting system (onco-pharmacovigilance) and creating awareness among health care professionals regarding the importance of ADR reporting may help prevent the problem.

Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies

Despite recent technological advancements and promising preclinical experiments, brain tumor patients are still met with limited treatment options. Some of the barriers to clinical improvements include the systemic toxicity of cytotoxic compounds, the impedance of the blood brain barrier (BBB), and the lack of therapeutic agents that can selectively target the intracranial tumor environment. To overcome such barriers, a number of chemotherapeutic agents and nucleic acid-based therapies are rapidly being synthesized and tested as new brain tumor-targeted delivery strategies. Novel carriers include liposomal and polymeric nanoparticles, wafers, microchips, microparticle-based nanoplatforms and cells-based vectors. Strong preclinical results suggest that these nanotechnologies are set to transform the therapeutic paradigm for brain tumor treatment. In addition to new tumoricidal agents, parallel work is also being conducted on the BBB front. Preclinical testing of chemical and physical modulation strategies is yielding improved intracranial concentrations. New diagnostic and therapeutic imaging techniques, such as high-intensity focused ultrasound and MRI-guided focused ultrasound, are being used to modulate the BBB in a more precise and non-invasive manner. This review details some of the tremendous advances that are being explored in current brain tumor targeted therapies, including local implant development, nanobiotechnology-based delivery strategies, and techniques of BBB manipulation.

ChemInform Abstract: Synthesis and Bioactivity of Antitubercular Peptides and Peptidomimetics: An Update

AbstractReview: 52 refs.

NKG2D and DNAM-1 Ligands: Molecular Targets for NK Cell-Mediated Immunotherapeutic Intervention in Multiple Myeloma.

A pivotal strategy to improve NK cell-mediated antitumor activity involves the upregulation of activating ligands on tumor cells. Enhancement of NK cell-mediated recognition of multiple myeloma cells was reported by us and others showing increased surface expression of NKG2D and DNAM-1 ligands on tumor cells following treatment with a number of chemotherapeutic agents, such as genotoxic drugs or inhibitors of proteasome, histone deacetylases, GSK3, and HSP-90. These compounds have the capability to affect tumor survival but also to activate specific transduction pathways associated with the upregulation of different NK cell activating ligands on the tumor cells. Here, we will summarize and discuss the molecular pathways whereby these drugs can regulate the expression of NK cell activating ligands in multiple myeloma cells.

Trypanosomatid Aquaporins: Roles in Physiology and Drug Response

In the class Kinetoplastida, we find an order of parasitic protozoans classified as Trypanosomatids. Three major pathogens form part of this order, Trypanosoma cruzi, Trypanosoma brucei, and Leishmania, which are responsible for disease and fatalities in millions of humans worldwide, especially in non-industrialized countries in tropical and sub-tropical regions. In order to develop new drugs and treatments, the physiology of these pathogenic protozoans has been studied in detail, specifically the significance of membrane transporters in host parasites interactions. Aquaporins and Aquaglyceroporins (AQPs) are a part of the major intrinsic proteins (MIPs) super-family. AQPs are characterized for their ability to facilitate the diffusion of water (aquaporin), glycerol (aquaglyceroporin), and other small-uncharged solutes. Furthermore, AQPs have been shown to allow the ubiquitous passage of some metalloids, such as trivalent arsenic and antimony. These trivalent metalloids are the active ingredient of a number of chemotherapeutic agents used against certain cancers and protozoan parasitic infections. Recently, the importance of the AQPs not only in osmotic adaptations but also as a factor in drug resistance of the trypanosomatid parasites has been reported. In this review, we will describe the physiological functions of aquaporins and their effect in drug response across the different trypanosomatids.