Chemotherapy Research and Practice
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Open Access journal
ISSN (Print) 2090-2107 - ISSN (Online) 2090-2115
Published by Hindawi [334 journals]
- Interferon-Gamma Improves Macrophages Function against M. tuberculosis in
Multidrug-Resistant Tuberculosis Patients
Abstract: Background. Mycobacterium tuberculosis (M. tuberculosis) that causes tuberculosis (TB) kills millions of infected people annually especially multidrug-resistant tuberculosis (MDR-TB). On infection, macrophages recognize the mycobacteria by toll-like receptor (TLR) followed by phagocytosis and control of mycobacteria. In addition, macrophages also secrete IL-12 to induce IFN-γ production by T, which, in turn, increases the phagocytosis and oxidative burst. Individuals with defects in innate or adaptive immunity exhibit increased susceptibility to M. tuberculosis. Understanding these immunologic mechanisms will help in TB control. We aimed to investigate the immunopathologic mechanisms in MDR-TB and role of recombinant human interferon-gamma (rhIFN-γ). Study Design and Methods. Monocyte-derived macrophages (MDMs) were generated from peripheral blood mononuclear cells of MDR-TB patients and healthy subjects and were investigated for immunologic response by ELISA and flow cytometry. Results. Different functional and molecular anomalies were observed in macrophages. In addition, a defective immune response to M. tuberculosis from the patient’s MDMs was characterized, which in turn improved by pretreatment with rhIFN-γ. Conclusion. This work highlights the fact that rhIFN-γ improves macrophages function against M. tuberculosis and treatment of patients with poor responsiveness to TB therapy may be needed in future to include IFN-γ as adjuvant therapy after the full characterization of pathological and molecular mechanisms in these and in other more multidrug-resistant TB patients.
PubDate: Tue, 12 Jul 2016 11:29:06 +000
- The Efficacy, Safety, and Cost Benefit of Olanzapine versus Aprepitant in
Highly Emetogenic Chemotherapy: A Pilot Study from South India
Abstract: Background. The efficacy, safety, and cost benefit of olanzapine (OLN) when compared to aprepitant (APR) in the prevention of chemotherapy induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC) were evaluated. Methods. A prospective pilot study was done in chemotherapy-naive patients receiving HEC to compare OLN versus APR along with palonosetron and dexamethasone. 100 patients consented to the protocol and were randomized and evaluated for Complete Response (CR) (no emesis, no rescue). Results. CR was 86% for the acute period, 86% for the delayed period, and 80% for the overall period in 50 patients receiving the APD regimen. CR was 84% for the acute period, 88% for the delayed period, and 78% for the overall period for 50 patients receiving the OPD regimen. Patients without nausea were APD: 88% acute, 84% delayed, and 84% overall, and OPD: 84% acute, 88% delayed, and 84% overall. There were no significant grade 3 or 4 toxicities. OPD was comparable to APD in the control of CINV. Conclusion. In this study, there was no significant difference between olanzapine and aprepitant in preventing CINV with highly emetogenic chemotherapy. Olanzapine may thus be used as a potential, safe, and cost beneficial alternative to prevent nausea and vomiting in HEC.
PubDate: Wed, 27 Jan 2016 14:28:08 +000
- Alternative Methods to Treat Nausea and Vomiting from Cancer Chemotherapy
Abstract: Chemotherapy Induced Nausea and Vomiting (CINV) is among the most intensive side effects and critical concerns for patients with cancer. Most of these patients experience nausea and vomiting after chemotherapy. Sometimes, this is so annoying that it may prevent them from continuing the therapy. With the recent advances, a variety of therapeutic methods are innovated and applied to control CINV. Among them, the main methods include medicinal therapy, relaxation, and herbal therapy. Yet, using dexamethasone together with massage therapy and ginger is identified as the most effective method.
PubDate: Sun, 08 Nov 2015 10:07:35 +000
- Oral Antineoplastic Agents: Assessing the Delay in Care
Abstract: The study was undertaken to determine the length of time between when a prescription for an oral antineoplastic agent is written by the provider and when the medication is received by the patient and to identify risk factors that significantly increase time to medication receipt. First-time fill prescriptions for oral antineoplastic agents were identified. The date the prescription was written and received by the patient was determined. A retrospective review was completed to gather additional information, including prescribed medication, indication, insurance coverage, patient assistance program use, dispensing pharmacy, and prior authorization requirements. The data was analyzed through multivariate statistical analysis and used to identify risk factors that may significantly increase the time to medication receipt. A total of 58 patients were included in the study. A median of 8 days elapsed between when the medication was prescribed and when it was received by the patient. Medication prescribed, absence of a Risk Evaluation Mitigation Strategies (REMS) program, and insurance type are factors that increased time to medication receipt. An understanding of the median time involved, as well as factors affecting the time to delivery of prescriptions, will help healthcare providers better plan and prepare for the use of oral antineoplastic agents.
PubDate: Wed, 28 Oct 2015 07:18:52 +000
- Using the Promise of Sonodynamic Therapy in the Clinical Setting against
Abstract: Sonodynamic therapy (SDT) is a form of ultrasound therapy in which specialized chemotherapeutic agents known as sonosensitizers are administered to increase the efficacy of ultrasound-mediated preferential damage of neoplastic cells. Multiple in vitro and in vivo studies have indicated that SDT has the ability to exhibit profound physical and chemical changes on cellular structure. As supportive as the data have been, assessment of this method at the clinical level has been limited to only solid tumors. Although SDT has shown efficacy against multiple adherent neoplastic cell lines, it has also shown particular promise with leukemia-derived cell lines. Potential procedures to administer SDT to leukemia patients are heating the appendages as ultrasound is applied to these areas (Heat and Treat), using an ultrasound probe to scan the body for malignant growths (Target and Destroy), and extracorporeal blood sonication (EBS) through dialysis. Each method offers a unique set of benefits and concerns that will need to be evaluated in preclinical mammalian models of malignancy before clinical examination can be considered.
PubDate: Tue, 25 Aug 2015 08:38:53 +000
- Aloe vera Gel: Effective Therapeutic Agent against Multidrug-Resistant
Pseudomonas aeruginosa Isolates Recovered from Burn Wound Infections
Abstract: Objective. Aloe vera is an herbal medicinal plant with biological activities, such as antimicrobial, anticancer, anti-inflammatory, and antidiabetic ones, and immunomodulatory properties. The purpose of this study was investigation of in vitro antimicrobial activity of A. vera gel against multidrug-resistant (MDR) Pseudomonas aeruginosa isolated from patients with burn wound infections. Methods. During a 6-month study, 140 clinical isolates of P. aeruginosa were collected from patients admitted to the burn wards of a hospital in Tehran, Iran. Antimicrobial susceptibility test was carried out against the pathogens using the A. vera gel and antibiotics (imipenem, gentamicin, and ciprofloxacin). Results. The antibiogram revealed that 47 (33.6%) of all isolates were MDR P. aeruginosa. The extract isolated from A. vera has antibacterial activity against all of isolates. Also, 42 (89.4%) isolates were inhibited by A. vera gel extract at minimum inhibitory concentration (MIC) 200 µg/mL. MIC value of A. vera gel for other isolates (10.6%) was 800 µg/mL. All of MDR P. aeruginosa strains were inhibited by A. vera at similar MIC50 and MIC90 200 µg/mL. Conclusion. Based on our results, A. vera gel at various concentrations can be used as an effective antibacterial agent in order to prevent wound infection caused by P. aeruginosa.
PubDate: Wed, 22 Jul 2015 11:35:12 +000
- Postchemotherapy Histopathological Evaluation of Ovarian Carcinoma: A
Abstract: Ovarian carcinomas are conventionally treated with primary debulking surgery followed by chemotherapy. Nowadays neoadjuvant chemotherapy followed by surgery is an upcoming treatment modality for ovarian carcinoma. This study highlights the histopathological changes observed after neoadjuvant chemotherapy. Present study is a 40-case study stressing five histological parameters: residual tumour, fibrosis, necrosis, inflammation, and psammoma bodies. All these parameters carry prognostic significance and they are easily reproducible. Fleiss kappa statistics were used to measure intraobserver agreement between pathologists which was found to be substantial to almost perfect with κ ranging between 0.621 and 1.00. This study highlights easily reproducible parameters and their incorporation in histopathology report, thus helping in patient management.
PubDate: Wed, 21 Jan 2015 10:13:27 +000
- Electron Microscopy in Rat Brain Slices Reveals Rapid Accumulation of
Cisplatin on Ribosomes and Other Cellular Components Only in Glia
Abstract: Cisplatin is a widely used, effective anticancer drug. Its use, however, is associated with several side effects including nephrotoxicity and neurotoxicity. It is known that cisplatin is accumulated in cells by the organic cation transport system and reacts with nucleotides, damaging them, but the precise target of cisplatin-induced neurotoxicity remains obscure. Here we report direct visualization of cisplatin inside brain cells using in vivo “cisplatin staining,” a technique that takes advantage of the high electron density of cisplatin, which contains platinum (). After applying 0.1% cisplatin to living brain slices for 30 min, we fixed the tissue and observed the accumulated cisplatin using electron microscopy. We found that cisplatin was localized mainly to ribosomes associated with endoplasmic reticulum (EPR) in glial cells and to the myelin sheath formed by oligodendrocytes around neuronal axons. Staining of nuclear DNA was moderate. Our in vivo “cisplatin staining” method validated that the main target of cisplatin is a direct attack on myelin and the RNA contained in ribosomes.
PubDate: Sun, 28 Dec 2014 09:58:06 +000
- Protective Effect of Quercetin on Melphalan-Induced Oxidative Stress and
Impaired Renal and Hepatic Functions in Rat
Abstract: One major challenge with the use of anticancer agents is the phenomenon of drug-induced toxicity. Melphalan (MPLN) is an alkylating anticancer agent, while quercetin (QCT) is an antioxidant. We investigated the protective role of quercetin against MPLN-induced toxicity. Twenty-five male Wistar rats (160–170 g) were randomized into five treatment groups; (I) control, (II) MPLN (0.2 mg/kg b.w.), (III) pre-treated with QCT (20 mg/kg b.w.) for 7 days followed by MPLN (0.2 mg/kg b.w.) for 7 days, (IV) cotreated with QCT (20 mg/kg b.w.) and MPLN (0.2 mg/kg b.w.) for 7 days, and (V) QCT (20 mg/kg b.w.) alone. MPLN caused a significant increase in plasma bilirubin, urea, and creatinine by 122.2%, 102.3%, and 188%, respectively (). Similarly, plasma ALP, ALT, AST, and γ-GT activities increased significantly by 57.9%, 144.3%, 71.3%, and 307.2%, respectively, relative to control. However, pre or cotreatment with QCT ameliorated the levels of renal and hepatic function indices. Hepatic ascorbic acid and GSH and activities of glutathione-S-transferase, SOD, and catalase decreased significantly by 36.2%, 188%, 46.5%, 34.4%, and 55.2%, respectively, followed by increase in MDA content by 46.5% relative to control. Pre- and cotreatment with QCT reestablished the hepatic antioxidant status and lipid peroxidation. Overall, quercetin protected against MPLN-induced renal and hepatic toxicity in rats.
PubDate: Thu, 11 Dec 2014 00:10:05 +000
- The Importance of Brain Metastasis in EGFR Mutation Positive NSCLC
Abstract: Introduction. Brain metastasis is a poor prognostic marker in lung cancer. However it is not known whether amongst patients with EGFR mutation those with brain metastases have a worse outcome. Methods. We compared the survival outcomes between EGFR mutation positive patients with and without brain metastases. In this retrospective analysis of prospective database of all metastatic lung cancer patients at our centre between July 2009 and December 2012, patients were treated with either combination chemotherapy or oral TKI. All patients with brain metastases received whole brain radiation. Kaplan Meier method was used for survival analysis and compared using log rank test. Results. 101 patients with EGFR mutated, metastatic lung cancer were studied. Fourteen had brain metastases and 87 did not. The common EGFR mutations were exon 19 deletion (61.3%) and exon 21 L858R mutation (28.7%). Overall response was 64% in extracranial metastasis group as compared to 50% in brain metastasis group. There was a significant worsening of median OS in the patients with brain metastases (11.6 months) compared with only extracranial metastases (18.7 months), . Conclusion. Amongst patients with EGFR mutant NSCLC, the presence of brain metastases leads to a worse outcome as compared to patients with extracranial metastases alone.
PubDate: Sun, 07 Dec 2014 09:38:06 +000
- Dose-Dense Epirubicin and Cyclophosphamide Followed by Weekly Paclitaxel
in Node-Positive Breast Cancer
Abstract: Background. Adding taxanes to anthracycline-based adjuvant chemotherapy has shown significant improvement in node-positive breast cancer patients but the optimal dose schedule has still remained undetermined. Objectives. The feasibility of dose-dense epirubicin in combination with cyclophosphamide (EC) followed by weekly paclitaxel as adjuvant chemotherapy in node-positive breast cancer patients was investigated. Methods. All patients were treated with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) every two weeks for four cycles with daily Pegfilgrastim (G-CSF) that was administered 3–10 days after each cycle of epirubicin and cyclophosphamide infusion which followed by (80 mg/m2) paclitaxel for twelve consecutive weeks. Results. Sixty consecutive patients were analyzed, of whom 57 patients (95%) completed the regimen and no case of toxicity-related death was observed. Grade 3/4 hematologic toxicity was uncommon and the most common grade 3/4 nonhematological adverse event was neuropathy disorders. Conclusions. Dose-dense epirubicin and cyclophosphamide followed by weekly paclitaxel with G-CSF support is a well-tolerated and feasible regimen in node-positive breast cancer patients without serious complications.
PubDate: Tue, 09 Sep 2014 00:00:00 +000
- Carbapenem Resistance among Enterobacter Species in a Tertiary Care
Hospital in Central India
Abstract: Objective. To detect genes encoding carbapenem resistance among Enterobacter species in a tertiary care hospital in central India. Methods. Bacterial identification of Enterobacter spp. isolates from various clinical specimens in patients admitted to intensive care units was performed by routine conventional microbial culture and biochemical tests using standard recommended techniques. Antibiotic sensitivity test was performed by standard Kirby Bauer disc diffusion technique. PCR amplification and automated sequencing was carried out. Transfer of resistance genes was determined by conjugation. Results. A total of 70/130 (53.84%) isolates of Enterobacter spp. were found to exhibit reduced susceptibility to imipenem (diameter of zones of inhibition ≤13 mm) by disc diffusion method. Among 70 isolates tested, 48 (68.57%) isolates showed MIC values for imipenem and meropenem ranging from 32 to 64 mg/L as per CLSI breakpoints. All of these 70 isolates were found susceptible to colistin in vitro as per MIC breakpoints (
PubDate: Sun, 10 Aug 2014 12:00:37 +000
- Imatinib: A Breakthrough of Targeted Therapy in Cancer
Abstract: Deregulated protein tyrosine kinase activity is central to the pathogenesis of human cancers. Targeted therapy in the form of selective tyrosine kinase inhibitors (TKIs) has transformed the approach to management of various cancers and represents a therapeutic breakthrough. Imatinib was one of the first cancer therapies to show the potential for such targeted action. Imatinib, an oral targeted therapy, inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT. Imatinib has also been proven to be effective in steroid-refractory chronic graft-versus-host disease because of its anti-PDGFR action. This paper is a comprehensive review of the role of Imatinib in oncology.
PubDate: Mon, 19 May 2014 07:16:29 +000
- Induction Chemotherapy in Technically Unresectable Locally Advanced
Carcinoma of Maxillary Sinus
Abstract: Background. Locally advanced carcinoma of maxillary sinus has been historically reported to have poor prognosis. We evaluated the role of NACT in improving the outcome in these patients. Methods. 41 patients with locally advanced technically unresectable (stage IVa) or unresectable maxillary carcinoma (stage IVb) were treated with induction chemotherapy between 2008 and 2011. The demographic profile, response and toxicity of chemotherapy, definitive treatment received, progression free survival (PFS), and overall survival (OS) were analyzed. Univariate and multivariate analysis were performed to determine factors associated with PFS and OS. Results. The chemotherapy included two drugs (platinum and taxane) in 34 patients (82.9%) and three drugs (platinum, taxane, and 5 FU) in 7 (17.1%). There was no complete response seen in any of the patients, stable disease in 18 (43.9%), partial response in 16 (39%), and progression in 7 (17.1%) patients. After induction, the treatment planned included surgery in 12 (29.3%), CT-RT in 24 (58.5%), radical RT in 1 (2.4%), palliative RT in 1 (2.4%), and palliative chemotherapy in 3 (7.3%) patients. Overall, the median PFS was 10.0 months. The OS at 24 months and 36 months was 41% and 35%, respectively. Conclusion. In unresectable maxillary carcinoma, induction chemotherapy has clinically significant benefit with acceptable toxicity.
PubDate: Sun, 11 May 2014 07:33:08 +000
- Ferric Carboxymaltose-Mediated Attenuation of Doxorubicin-Induced
Cardiotoxicity in an Iron Deficiency Rat Model
Abstract: Since anthracycline-induced cardiotoxicity (AIC), a complication of anthracycline-based chemotherapies, is thought to involve iron, concerns exist about using iron for anaemia treatment in anthracycline-receiving cancer patients. This study evaluated how intravenous ferric carboxymaltose (FCM) modulates the influence of iron deficiency anaemia (IDA) and doxorubicin (3–5 mg per kg body weight [BW]) on oxidative/nitrosative stress, inflammation, and cardiorenal function in spontaneously hypertensive stroke-prone (SHR-SP) rats. FCM was given as repeated small or single total dose (15 mg iron per kg BW), either concurrent with or three days after doxorubicin. IDA (after dietary iron restriction) induced cardiac and renal oxidative stress (markers included malondialdehyde, catalase, Cu,Zn-superoxide dismutase, and glutathione peroxidase), nitrosative stress (inducible nitric oxide synthase and nitrotyrosine), inflammation (tumour necrosis factor-alpha and interleukin-6), and functional/morphological abnormalities (left ventricle end-diastolic and end-systolic diameter, fractional shortening, density of cardiomyocytes and capillaries, caveolin-1 expression, creatinine clearance, and urine neutrophil gelatinase-associated lipocalin) that were aggravated by doxorubicin. Notably, iron treatment with FCM did not exacerbate but attenuated the cardiorenal effects of IDA and doxorubicin independent of the iron dosing regimen. The results of this model suggest that intravenous FCM can be used concomitantly with an anthracycline-based chemotherapy without increasing signs of AIC.
PubDate: Wed, 30 Apr 2014 07:51:24 +000
- A Postauthorization Survey to Document the Therapeutic Management of
Oxaliplatin as a First-Line Chemotherapy Regimen in South Africa in
Patients with Metastatic Colorectal Cancer
Abstract: Oxaliplatin is a standard first-line treatment for metastatic colorectal cancer. The objectives were to document the therapeutic management of oxaliplatin in South Africa, determine the incidence and severity of sensory neuropathy, and record the 2-year survival rate. Meccelox was a prospective, noncontrolled, open label, multicentre, observational survey of adult patients with stage IV metastatic colorectal cancer treated with oxaliplatin-based chemotherapeutic regimens. The study was conducted from August 2007 to November 2011 in 29 sites in South Africa by 66 participating treating physicians. Among the 195 enrolled patients, 61% were treated with FOLFOX regimen (5-fluorouracil/folinic acid plus oxaliplatin) for an average of 12 cycles and 32% patients were treated with XELOX (capecitabine plus oxaliplatin) for an average of 6–8 cycles, with the main reason for discontinuation being completion of the preplanned prescribed regimen. In Meccelox survey, 80% of patients were treated with intent of palliation. Overall 64% of patients reported symptoms of sensory neuropathy. The 2-year survival rate was 30%. Conclusions. Patients received a specified preplanned number of chemotherapy cycles rather than being treated until disease progression or toxicity. Both the incidence of neuropathy and the 2-year survival rate were less than previous reports.
PubDate: Thu, 10 Apr 2014 10:24:10 +000
- Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma
Treated with Different Schedules of FOLFOX
Abstract: The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (), whereas frequency and onset of peripheral neuropathy were highly significant () in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m2), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m2) after few treatment cycles.
PubDate: Sun, 29 Sep 2013 09:01:31 +000
- Self-Management of Oxaliplatin-Related Peripheral Neuropathy in Colorectal
Abstract: Purpose. The purpose of this study was to evaluate medications that cancer survivors with oxaliplatin-induced peripheral neuropathy take to control neuropathic symptom, and to explore self-management techniques used at home to provide temporary relief of painful neuropathy. This was a mixed methods, descriptive, cross-sectional study using self-reported data from colorectal cancer survivors previously treated with oxaliplatin. We analyzed demographic and medication data obtained from participants, along with written comments from an open-ended question regarding methods participants had tried to self-manage symptoms of neuropathy. Results. Twenty-nine percent of the sample reported taking some type of nutritional supplement with potential neuroprotective qualities. Opioids were being taken by 10% of the sample, and nonsteroidal anti-inflammatory and over-the-counter medications were taken by 15% of participants. Twelve percent of participants were taking antidepressants and 10% were taking anticonvulsants, primarily gabapentin. Recurrent themes for nonpharmacologic treatment included avoiding the cold/keeping warm, keeping moving, massaging or rubbing the affected area, and living with it. Conclusions. Patients treated with oxaliplatin for colorectal cancer utilize a variety of traditional pharmacologic agents and nutritional supplements in an effort to self-manage neuropathic symptoms. Patients also employ a variety of home-based therapies to provide temporary relief of peripheral neuropathy symptoms.
PubDate: Sun, 25 Aug 2013 09:26:15 +000
- Identification of Functional Regulatory Residues of the β-Lactam
Inducible Penicillin Binding Protein in Methicillin-Resistant
Abstract: Resistance to methicillin by Staphylococcus aureus is a persistent clinical problem worldwide. A mechanism for resistance has been proposed in which methicillin resistant Staphylococcus aureus (MRSA) isolates acquired a new protein called β-lactam inducible penicillin binding protein (PBP-2′). The PBP-2′ functions by substituting other penicillin binding proteins which have been inhibited by β-lactam antibiotics. Presently, there is no structural and regulatory information on PBP-2′ protein. We conducted a complete structural and functional regulatory analysis of PBP-2′ protein. Our analysis revealed that the PBP-2′ is very stable with more hydrophilic amino acids expressing antigenic sites. PBP-2′ has three striking regulatory points constituted by first penicillin binding site at Ser25, second penicillin binding site at Ser405, and finally a single metallic ligand binding site at Glu657 which binds to ions. This report highlights structural features of PBP-2′ that can serve as targets for developing new chemotherapeutic agents and conducting site direct mutagenesis experiments.
PubDate: Mon, 29 Jul 2013 12:04:30 +000
- High-Dose Interleukin-2 (HD IL-2) Therapy Should Be Considered for
Treatment of Patients with Melanoma Brain Metastases
Abstract: A retrospective review was performed on patients with stable melanoma brain metastases treated with HD IL-2 therapy (720,000 IU/kg per dose intravenously; 14 doses, 2 cycles per course, maximum 2 courses) from January 1999 to June 2011 at Saint Louis University. There were 5 men and 3 women; median age was 52.2 years (26.8–61.1 years). One patient started treatment with lung lesions only (after resection of melanoma brain disease) and experienced partial response. Seven patients had brain metastases at treatment initiation. Median overall survival (mOS) for entire cohort () was 8.7 months (2.1 to 19.0 months). All patients with brain metastases at first dose () showed progressive disease; mOS was 6.7 months (range 2.1–18.2 months) for this group. Patients received radiosurgery and whole brain radiation before and after HD IL-2 therapy. One patient had symptoms suggestive of neurotoxicity. A history of alcohol abuse was revealed during admission. The patient's symptoms improved with initiation of an alcohol withdrawal protocol. In this analysis, patients with melanoma brain metastases received HD IL-2 without treatment-related mortality. We think that HD IL-2 should be considered as a treatment option in patients with melanoma brain metastases who are otherwise eligible for therapy.
PubDate: Mon, 13 May 2013 08:25:10 +000
- Lomustine Analogous Drug Structures for Intervention of Brain and Spinal
Cord Tumors: The Benefit of In Silico Substructure Search and Analysis
Abstract: Lomustine is a nitrosourea anticancer agent shown to be effective for treatment of childhood medulloblastoma. In silico substructure searches produced 17 novel nitrosourea agents analogous to lumustine and retaining activity for DNA alkylation and cytotoxic activity. The mean values for Log P, polar surface area, formula weight, number of oxygens & nitrogens, and rotatable bonds were 2.524, 62.89 Anstroms2, 232.8, 5, and 2, respectively. All 17 agents have formula weight less than 450 and Log P less than 5, two criteria preferred for blood-brain barrier penetration. These agents have a polar surface area less than 90 Angstroms2. Each show zero violations of the Rule of five indicating favorable drug likeness and oral drug activity. Hierarchical cluster analysis indicated that 16 of the novel agents were highly similar to lomustine, save for agent 12 which bears a hydroxylated branched carbon substituent. A total of 17 novel anticancer agents were elucidated having molecular properties very effective for penetrating through the BBB and into the central nervous system. This study shows the effectiveness of in silico search and recognition of anticancer agents that are suitable for the clinical treatment of brain tumors.
PubDate: Tue, 16 Apr 2013 11:28:13 +000
- Neoadjuvant Chemotherapy prior to Radical Prostatectomy for Patients with
High-Risk Prostate Cancer: A Systematic Review
Abstract: High-risk prostate cancer represents a pretentious clinical problem since a significant number of its patients will relapse and progress after radical prostatectomy. Neoadjuvant chemotherapy may be valuable since its efficacy in hormone-resistant prostate cancer has been established. In this paper, we report studies of neoadjuvant chemotherapies that have been used in high-risk patients prior to radical prostatectomy. Even though the results regarding the prognostic surrogates are not significant, the effects on clinical and pathological outcomes are promising, while toxicity in most of the studies is in the expected field.
PubDate: Thu, 21 Feb 2013 13:51:29 +000
- Inhibition of NF-κB by Dehydroxymethylepoxyquinomicin Suppresses Invasion
and Synergistically Potentiates Temozolomide and γ-Radiation Cytotoxicity
in Glioblastoma Cells
Abstract: Despite advances in neurosurgery and aggressive treatment with temozolomide (TMZ) and radiation, the overall survival of patients with glioblastoma (GBM) remains poor. Vast evidence has indicated that the nuclear factor NF-κB is constitutively activated in cancer cells, playing key roles in growth and survival. Recently, Dehydroxymethylepoxyquinomicin (DHMEQ) has shown to be a selective NF-κB inhibitor with antiproliferative properties in GBM. In the present study, the ability of DHMEQ to surmount tumor's invasive nature and therapy resistance were further explored. Corroborating results showed that DHMEQ impaired cell growth in dose- and time-dependent manners with G2/M arrest when compared with control. Clonogenicity was also significantly diminished with increased apoptosis, though necrotic cell death was also observed at comparable levels. Notably, migration and invasion were inhibited accordingly with lowered expression of invasion-related genes. Moreover, concurrent combination with TMZ synergistically inhibited cell growth in all cell lines, as determined by proliferation and caspase-3 activation assays, though in those that express O6-methylguanine-DNA methyltransferase, the synergistic effects were schedule dependent. Pretreatment with DHMEQ equally sensitized cells to ionizing radiation. Taken together, our results strengthen the potential usefulness of DHMEQ in future therapeutic strategies for tumors that do not respond to conventional approaches.
PubDate: Thu, 21 Feb 2013 10:25:47 +000
- Monoclonal Antibodies against Epidermal Growth Factor Receptor in Solid
PubDate: Mon, 24 Dec 2012 10:54:25 +000
- The HER2 Receptor in Breast Cancer: Pathophysiology, Clinical Use, and New
Advances in Therapy
Abstract: Human epidermal growth factor receptor 2 (HER2) is overexpressed in around 20–30% of breast cancer tumors. It is associated with a more aggressive disease, higher recurrence rate, and increased mortality. Trastuzumab is a HER2 receptor blocker that has become the standard of care for the treatment of HER2 positive breast cancer. The effectiveness of Trastuzumab has been well validated in research as well as in clinical practice. The addition of Trastuzumab to standard of care chemotherapy in clinical trials has been shown to improve outcomes for early stage as well as metastatic HER2 positive breast cancer. The most clinically significant side effect of Trastuzumab is the risk of cardiac myocyte injury, leading to the development of congestive heart failure. The emergence of patterns of resistance to Trastuzumab has led to the discovery of new monoclonal antibodies and other targeted agents aimed at overcoming Trastuzumab resistance and improving survival in patients diagnosed with HER2 positive breast cancers.
PubDate: Thu, 20 Dec 2012 17:35:50 +000
- Chemotherapy and Dietary Phytochemical Agents
Abstract: Chemotherapy has been used for cancer treatment already for almost 70 years by targeting the proliferation potential and metastasising ability of tumour cells. Despite the progress made in the development of potent chemotherapy drugs, their toxicity to normal tissues and adverse side effects in multiple organ systems as well as drug resistance have remained the major obstacles for the successful clinical use. Cytotoxic agents decrease considerably the quality of life of cancer patients manifesting as acute complaints and impacting the life of survivors also for years after the treatment. Toxicity often limits the usefulness of anticancer agents being also the reason why many patients discontinue the treatment. The nutritional approach may be the means of helping to raise cancer therapy to a new level of success as supplementing or supporting the body with natural phytochemicals cannot only reduce adverse side effects but improve also the effectiveness of chemotherapeutics. Various plant-derived compounds improve the efficiency of cytotoxic agents, decrease their resistance, lower and alleviate toxic side effects, reduce the risk of tumour lysis syndrome, and detoxify the body of chemotherapeutics. The personalised approach using various phytochemicals provides thus a new dimension to the standard cancer therapy for improving its outcome in a complex and complementary way.
PubDate: Thu, 20 Dec 2012 14:07:29 +000
- Advances in Targeting HER3 as an Anticancer Therapy
Abstract: HER3 (ErbB3) is a unique member of the human epidermal growth factor receptor (EGFR) family (ErbB family). It functions only through dimerization with other members of the ErbB family and modulates activity and sensitivity to targeted cancer therapies. This paper briefly describes the mechanism of HER3 in signal transduction and its potential role in acquired resistance to EGFR- and HER2-targeted therapies. We also consider recent developments in HER3-targeting therapeutics and their combination with inhibitors of other ErbB members in clinical applications.
PubDate: Wed, 07 Nov 2012 16:16:50 +000
- Novel Drugs Targeting the Epidermal Growth Factor Receptor and Its
Downstream Pathways in the Treatment of Colorectal Cancer: A Systematic
Abstract: Colorectal cancer is the second most common malignancy among men and women in the United States, and the 5-year survival rate remains poor despite recent advances in chemotherapy and targeted agents. The mainstay of therapy for advanced disease remains the cytotoxic chemotherapy including 5-FU, irinotecan, and oxaliplatin. The USFDA approval and introduction of targeted therapies, including cetuximab and panitumumab (monoclonal antibodies targeting the epidermal growth factor receptor (EGFR)) and bevacizumab (monoclonal antibody targeting the vascular epithelial growth factor (VEGF)), has improved the median survival of patients with metastatic colorectal cancer to around 24 months. Clearly, better and more efficacious drugs are needed, and target-specific agents remain the future of cancer treatment. On this front, rapid advances are being made, which are likely to change the future of the management of metastatic colorectal cancer. However, absence of specific biomarkers for the use of targeted agents, in the subset of population who will benefit from the treatment, remains a major drawback. In this paper, we review agents that are in phases 1 and 2 clinical development, specifically targeting the EGFR and its subsequent downstream pathways.
PubDate: Sun, 14 Oct 2012 16:45:18 +000
- Antiepidermal Growth Factor Receptor Monoclonal Antibodies: Applications
in Colorectal Cancer
Abstract: Patients with metastatic colorectal cancer have a poor prognosis and present a challenge to clinicians. The role of the antiepidermal growth factor receptor (EGFR) pathway in tumorogenesis and tumor progression has been well defined. This paper will review the use of anti-EGFR monoclonal antibodies in the treatment of operable, as well as metastatic colorectal cancer both in the setting of KRAS mutation unselected patients and later in KRAS wild-type patients. Active investigations designed to further identify predictive biomarkers that may be potentially druggable are reviewed as well.
PubDate: Mon, 08 Oct 2012 11:18:21 +000
- The Use of Epidermal Growth Factor Receptor Monoclonal Antibodies in
Squamous Cell Carcinoma of the Head and Neck
Abstract: Targeting of the EGF receptor (EGFR) has become a standard of care in several tumor types. In squamous cell carcinoma of the head and neck, monoclonal antibodies directed against EGFR have become a regular component of therapy for curative as well as palliative treatment strategies. These agents have anti-tumor efficacy as a single modality and have demonstrated synergistic tumor killing when combined with radiation and/or chemotherapy. While cetuximab has been the primary anti-EGFR monoclonal antibody used in the US, variant anti-EGFR monoclonal antibodies have been used in several clinical studies and shown benefit with improved toxicity profiles. Next generation anti-EGFR monoclonal antibodies may demonstrate multi-target epitope recognition, enhanced immune cell stimulation, or conjugation with radioisotopes in order to improve clinical outcomes. Identification of the specific patient subset that would optimally benefit from anti-EGFR monoclonal antibodies remains an elusive goal.
PubDate: Tue, 02 Oct 2012 14:09:11 +000