Publication date: December 2017
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Yassine Lalami, Jean Klastersky
Despite the overwhelming evidence for the role of granulocyte colony stimulating factors (G-CSF) in managing febrile neutropenia (FN) risk, chemotherapy-induced neutropenia (CIN) and/or FN still remain the most common reasons for reducing relative dose intensity (RDI) and/or delaying chemotherapy schedule. The need to maintain RDI to ensure optimal clinical outcomes is one of the key rationales for utilizing G-CSF. There is a high incidence of reduced RDI in both curative and palliative settings, and this observation is especially evidenced in retrospective analyses. Reduced RDI leads to significantly decreased survival outcomes and quality of life in various malignancies at various clinical settings and stages.Beyond its role as a surrogate prognostic marker, high-grade CIN may have an unexpected predictive role in clinical practice, as illustrated by several data relating CIN occurrence with favorable survival outcomes; this may be due to the fact that body surface area (BSA) – based calculation of dose may not fully account for the pharmacokinetics (PK) of cytotoxic drugs and the fact that there may be variability in drug metabolism between patients treated with same chemotherapy regimens.
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 18 Νοεμβρίου 2017
Impact of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) on cancer treatment outcomes: An overview about well-established and recently emerging clinical data
Biomarkers in Prostate Cancer – Current Clinical Utility and Future Perspectives
Source:Critical Reviews in Oncology/Hematology
Author(s): Alexander Kretschmer, Derya Tilki
Current tendencies in the treatment course of prostate cancer patients increase the need for reliable biomarkers that help in decision-making in a challenging clinical setting. Within the last decade, several novel biomarkers have been introduced. In the following comprehensive review article, we focus on diagnostic (PHI®, 4K score, SelectMDx®, ConfirmMDx®, PCA3, MiPS, ExosomeDX, mpMRI) and prognostic (OncotypeDX GPS®, Prolaris®, ProMark®, DNA-ploidy, Decipher®) biomarkers that are in widespread clinical use and are supported by evidence. Hereby, we focus on multiple clinical situations in which innovative biomarkers may guide decision-making in prostate cancer therapy. In addition, we describe novel liquid biopsy approaches (circulating tumour cells, cell-free DNA) that have been described as predictive biomarkers in metastatic castration-resistant prostate cancer and might support an individual patient-centred oncological approach in the nearer future.
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Optimization and purification of l-asparaginase from fungi: A systematic review
Source:Critical Reviews in Oncology/Hematology
Author(s): Paula Monteiro Souza, Marcela Medeiros de Freitas, Samuel Leite Cardoso, Adalberto Pessoa, Eliete Neves Silva Guerra, Pérola Oliveira Magalhães
The purpose of this systematic review was to identify the available literature of the l-asparaginase producing fungi. This study followed the Preferred Reporting Items for Systematic Reviews. The search was conducted on five databases: LILACS, PubMed, Science Direct, Scopus and Web of Science up until July 20th, 2016, with no time or language restrictions. The reference list of the included studies was crosschecked and a partial gray literature search was undertaken. The methodology of the selected studies was evaluated using GRADE. Asparaginase production, optimization using statistical design, purification and characterization were the main evaluated outcomes. Of the 1,686 initially gathered studies, 19 met the inclusion criteria after a two-step selection process. Nine species of fungi were reported in the selected studies, out of which 13 studies optimized the medium composition using statistical design for enhanced asparaginase production and six reported purification and characterization of the enzyme. The genera Aspergillus were identified as producers of asparaginase in both solid and submerged fermentation and l-asparagine was the amino acid most used as nitrogen source. This systematic review demonstrated that different fungi produce l-asparaginase, which possesses a potential in leukemia treatment. However, further investigations are required to confirm the promising effect of these fungal enzymes.
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Concomitant Use Of Corticosteroids And Immune Checkpoint Inhibitors In Patients With Hematologic Or Solid Neoplasms: A Systematic Review
Source:Critical Reviews in Oncology/Hematology
Author(s): A. Garant, C. Guilbault, T. Ekmekjian, Z. Greenwald, P. Murgoi, T. Vuong
PurposeClinical trials studying immune checkpoint inhibitors exclude patients on corticosteroids, due to the hypothesis that corticosteroids may antagonize immunotherapy. We performed a systematic review of the literature looking at the clinical outcomes of cancer patients treated with immune checkpoint inhibitors and concomitant corticosteroids.MethodsThe following databases were searched for relevant studies: MEDLINE, Embase Classic+Embase, BIOSIS Previews, the Cochrane Database of Systematic Reviews, the CENTRAL Registry of Controlled Trials, Web of Science and Scopus. Abstracts from the meetings of the European Cancer Congress/European Society for Medical Oncology, the American Society of Clinical Oncology, the American Society of Hematology, the European Society for Radiotherapy & Oncology, the American Society for Radiation Oncology and the European Society for Radiotherapy & Oncology were manually searched. Two independent reviewers screened the references: case reports and articles with a low risk of bias were retained.ResultsFollowing a retrieval of 14603 unique references, 140 abstracts were retained for review; 27 articles are in the final analysis. Although limited, the reviewed data suggests that the concomitant administration of corticosteroids and immune checkpoint inhibitors may not necessarily lead to poorer clinical outcomes.ConclusionIn our systematic review, there was no objective data on the exact types of corticosteroids and the dose threshold above which an interaction could be measured clinically. Consideration of stratified randomization and treatment sequence evaluations in prospective trials may clarify this challenging topic and perhaps improve patient access to immune checkpoint therapies.
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The predictive value of primary tumor location in patients with metastatic colorectal cancer: A systematic review
Publication date: Available online 7 November 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Nele Boeckx, Katleen Janssens, Guy Van Camp, Marika Rasschaert, Konstantinos Papadimitriou, Marc Peeters, Ken Op de Beeck
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. It has been reported that left- and right-sided CRC harbor varying disease characteristics, which leads to a difference in prognosis and response to therapy. Recently, there have been retrospective studies about tumor location in metastatic CRC (mCRC) and its potential to predict the effect of anti-vascular endothelial growth factor and anti-epidermal growth factor receptor (anti-EGFR) therapies. In this review, we provide a comprehensive overview of the latest trials studying the predictive value of primary tumor location in mCRC and discuss biomarkers that might be associated with the differences in treatment response. Although data need to be interpreted with caution due to the absence of randomized trials stratified based on tumor location, patients with left-sided CRC seem to benefit more from anti-EGFR therapy than patients with right-sided CRC. Further clinical trials, stratified for tumor location, are warranted.
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Ovarian sex-cord stromal tumours and small cell tumours: pathological, genetic and management aspects
Source:Critical Reviews in Oncology/Hematology
Author(s): Stergios Boussios, Michelle Moschetta, George Zarkavelis, Alexandra Papadaki, Aristides Kefas, Konstantina Tatsi
Non-epithelial ovarian cancers (NEOC) constitute a group of uncommon malignancies and their treatment is still a challenging task. Collectively, these tumours account for about 10% of all ovarian cancers and occur in all age groups from childhood to old-age. They include malignancies of germ cell origin, sex cord-stromal cell origin, and a variety of extremely rare ovarian cancers, such as small-cell carcinomas and sarcomas. Each of these classifications encompasses multiple histologic subtypes. It is imperative that these rare tumours are managed with accurate diagnosis, staging, and treatment, to optimise the outcome. The aetiology and molecular origins of each sub-group of NEOC remain largely unresolved, and international cooperation to promote high quality translational research is crucial. Much effort has been made into researching the molecular mechanisms underlying epithelial ovarian cancers, but far less is known about the genetic changes in NEOC. In this article, it is provided an overview of the current knowledge on the incidence, clinical presentation, pathology, genetics, therapeutic interventions, survival and prognostic factors of adult and juvenile granulosa cell tumours (GrCT), Sertoli-Leydig Cell tumours (SLCT) and small cell carcinoma of the ovary. We also consider future potential therapeutic targets in these rare cancers.
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Effects of exercise on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: A systematic review
Source:Critical Reviews in Oncology/Hematology
Author(s): Duregon Federica, Vendramin Barbara, Bullo Valentina, Gobbo Stefano, Cugusi Lucia, Di Blasio Andrea, Neunhaeuserer Daniel, Zaccaria Marco, Bergamin Marco, Ermolao Andrea
BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological and clinically relevant side effect of many commonly used chemotherapeutic agents. Moreover, little effort has been done to investigate the potentially beneficial effects of specific exercises to counteract the CIPN symptoms.ObjectiveThis document aims to summarize and analyze systematically the current body of evidence about the effects of specific exercise protocols on CIPN symptoms, balance control, physical function and quality of life in patients with CIPN.Literature surveySpecific terms were identified for the literature research in MEDLINE, Scopus, Bandolier, PEDro, and Web of Science.MethodologyFour manuscripts were considered eligible for this review. Quality appraisal distinguished two studies as high quality investigations while two with low quality. Results were summarized in the following domains: "CIPN symptoms", "Static balance control", "Dynamic balance control", "Quality of life and Physical function".SynthesisSignificant improvements were detected on postural control. Additionally, patients' quality of life and independence were found ameliorated after exercise sessions. Combined exercise protocols including endurance, strength and sensorimotor training showed larger improvements.ConclusionsThis systematic review comes from a highly selected but small source of data. Nevertheless, specific exercise for cancer patients undergoing chemotherapy with CIPN symptoms should be recommended since these interventions appeared as feasible and have been demonstrated as useful tools to counteract some of the limitations due to chemotherapy.
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Editorial Board
Publication date: November 2017
Source:Critical Reviews in Oncology/Hematology, Volume 119
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Erratum to “Systematic literature review of health-related quality of life in locally-advanced non-small cell lung cancer: Has it yet become state-of-the-art?” [Crit. Rev. Oncol. Hematol., 119 (November) (2017) 40–49]
Source:Critical Reviews in Oncology/Hematology
Author(s): Lotte van der Weijst, Veerle Surmont, Wim Schrauwen, Yolande Lievens
http://ift.tt/2mFZ0pt
Fertility management for malignant ovarian germ cell tumors patients
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Chiara Di Tucci, Assunta Casorelli, Elisa Morrocchi, Innocenza Palaia, Ludovico Muzii, Pierluigi Benedetti Panici
Malignant Germ Cell Tumors have primarily affecting adolescents and young adults. In advanced disease, greater than 70% of patients can be cured with standard chemotherapy regimens and fertility-sparing surgery appears to be safe with excellent survival after long-term follow-up.Due to their rarity, follow up and fertility management is largely based on trials of epithelial ovarian cancer or on few small studies.We report a review of the literature studies about the assessment, the monitoring and the treatment of fertility for Malignant Germ Cell Tumors as pratical guidelines for management of fertility in these patients.
http://ift.tt/2mEjDlN
Management of salivary gland malignant tumor: The policlinico Umberto I, sapienza university of rome head and neck unit clinical recommendations
Publication date: Available online 27 October 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Francesca De Felice, Marco de incentiis, Valentino Valentini, Daniela Musio, Silvia Mezi, Luigi Lo Mele, Marco Della Monaca, Vittorio D'Aguanno, Valentina Terenzi, Martina Di Brino, Edoardo Brauner, Nadia Bulzonetti, Gianluca Tenore, Giulia Pomati, Andrea Cassoni, Mario Tombolini, Andrea Battisti, Antonio Greco, Giorgio Pompa, Antonio Minni, Umberto Romeo, Enrico Cortesi, Antonella Polimeni, Vincenzo Tombolini
Salivary gland malignant tumor (SGMT) is a malignant disease requiring multidisciplinary approach. The rare incidence and the consequent lack of robust evidence-based medicine has called for a comprehensive update to draw recommendations for clinical practice. This paper is a summary of the XXX Head and Neck Unit guidelines regarding the management of SGMT. Recommendations include the indications for exclusive and adjuvant therapy, as well as metastatic management, for both major and minor SGMT.
http://ift.tt/2zfFiqq
Incidence of skin toxicity in squamous cell carcinoma of the head and neck treated with radiotherapy and cetuximab: A systematic review
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Pierluigi Bonomo, Mauro Loi, Isacco Desideri, Emanuela Olmetto, Camilla Delli Paoli, Francesca Terziani, Daniela Greto, Monica Mangoni, Silvia Scoccianti, Gabriele Simontacchi, Giulio Francolini, Icro Meattini, Saverio Caini, Lorenzo Livi
PurposeRadiotherapy plus cetuximab is an effective combination therapy for locally advanced head and neck squamous cell carcinoma. The aim of our study was to determine the frequency of skin toxicity in patients receiving the combined treatment.ResultsForty-eight studies were included in our analysis, for a total of 2152 patients. The mean rates of G3/G4 radiation dermatitis and acneiform rash were 32.5% (SD: 20.4; 95% CI: 28.5–36.5) and 13.4% (SD: 11.5; 95% CI: 11.2–15.6), respectively. The majority of studies referred to CTCAE scales for reporting both side effects (85.7% and 92.1%, respectively). Data on the management of skin toxicity were available in only 35.4% of the reviewed literature.Conclusionssevere radiation dermatitis is a frequent side effect induced by the combination of radiotherapy and cetuximab in head and neck cancer. The lack of predictive biomarkers of toxicity hampers the possibilty to design preventive measures on a personalized basis.
http://ift.tt/2mFYTdx
The effects of enzalutamide and abiraterone on skeletal related events and bone radiological progression free survival in castration resistant prostate cancer patients: An indirect comparison of randomized controlled trials
Source:Critical Reviews in Oncology/Hematology
Author(s): Sergio Rizzo, Antonio Galvano, Francesco Pantano, Michele Iuliani, Bruno Vincenzi, Francesco Passiglia, Silvia Spoto, Giuseppe Tonini, Viviana Bazan, Antonio Russo, Daniele Santini
Two new drugs, the CYP17 inhibitor abiraterone acetate and the androgen receptor (AR) antagonist enzalutamide, have recently shown to prolong OS prior chemotherapy or in docetaxel treated mCRPC patients, using steroidal therapy or placebo as control group. Updated analyses underlined the role of these new agents on two prostate-specific endpoints as radiographic progression-free survival (rPFS) and time to first skeletal-related event (tSRE). On the basis of these reports, we made an indirect comparison between abiraterone and enzalutamide. We obtained a clinically but not significant difference favouring enzalutamide over abiraterone in terms of rPFS (HR 0.48, 95% CI 0.22–1.02). No significant difference was shown in term of tSRE (HR 0.99, 95% CI 0.83–1.17). In conclusion, abiraterone and enzalutamide have both demonstrated to significantly delay the bone progression resulting in similar improvements in bone-related endpoints in patients with mCRPC.
http://ift.tt/2zgyCYU
Developing chemotherapy for diffuse pontine intrinsic gliomas (DIPG)
Publication date: December 2017
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Ho-Shin Gwak, Hyeon Jin Park
Prognosis of diffuse intrinsic pontine glioma (DIPG) is poor, with a median survival of 10 months after radiation. At present, chemotherapy has failed to show benefits over radiation.Advances in biotechnology have enabled the use of autopsy specimens for genomic analyses and molecular profiling of DIPG, which are quite different from those of supratentorial high grade glioma. Recently, combined treatments of cytotoxic agents with target inhibitors, based on biopsied tissue, are being examined in on-going trials. Spontaneous DIPG mice models have been recently developed that is useful for preclinical studies. Finally, the convection-enhanced delivery could be used to infuse drugs directly into the brainstem parenchyma, to which conventional systemic administration fails to achieve effective concentration.The WHO glioma classification defines a diffuse midline glioma with a H3-K27M-mutation, and we expect increase of tissue confirmation of DIPG, which will give us the biological information helping the development of a targeted therapy.
http://ift.tt/2xKST4c
ERCC1 as a prognostic factor for survival in patients with advanced urothelial cancer treated with platinum based chemotherapy: A systematic review and meta-analysis
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Yuksel Urun, Jeffrey J. Leow, Andre P. Fay, Laurence Albiges, Toni K. Choueiri, Joaquim Bellmunt
BackgroundThe predictive role of excision repair cross-complementing group 1 (ERCC1) as a predictive factor in patients with advanced urothelial cancer (AUC) treated with platinum-based treatment is not well defined. Here, we evaluate the role of ERCC1 in patients with AUC treated with platinum-based treatment.MethodsWe performed comprehensive, systematic computerized search to identify relevant studies through Medline, Embase, Cochrane Controlled Trials Register (CCTR) databases and abstracts from American Society of Clinical Oncology (ASCO) and ASCO Genitourinary Cancers Symposium, European Society For Medical Oncology (ESMO) and European Association of Urology (EAU) meeting up to July 2015. A systematic review and meta-analysis were performed.ResultsWe included a total of 1475 patients from 13 studies. We found that ERCC1 positivity was significantly associated with worse progression-free survival (pooled HR: 1.54, 95% CI: 1.13–2.11, p=0.006). There was no significant association with overall survival (pooled HR1.63, 95% CI: 0.93–2.88, p=0.09) and disease-free survival (pooled HR: 1.092, 95% CI: 0.63–1.90, p=0.75).ConclusionERCC1 positivity might be a prognostic indicator for poorer survival outcomes among patients with AUC. ERCC1 positivity was trending to poorer OS but was statistically worse for PFS. Further large prospective studies are warranted as ERCC1 could be used as a predictive marker to direct treatment of patients with AUC.
http://ift.tt/2zfFd66
The role of Nuclear Factor-kappa B signaling in human cervical cancer
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Sam Tilborghs, Jerome Corthouts, Yannick Verhoeven, David Arias, Christian Rolfo, Xuan Bich Trinh, Peter A. van Dam
Background The Nuclear Factor kappaB (NF-kB) family consists of transcription factors that play a complex and essential role in the regulation of immune responses and inflammation. NF-kB has recently generated considerable interest as it has been implicated in human cancer initiation, progression and resistance to treatment. In the present comprehensive review the different aspects of NF-kB signaling in the carcinogenesis of cancer of the uterine cervix are discussed. NF-kB functions as part of a network, which determines the pattern of its effects on the expression of several other genes (such as crosstalks with reactive oxygen species, p53, STAT3 and miRNAS) and thus its function. Activation of NF-kB triggered by a HPV infection is playing an important role in the innate and adaptive immune response of the host. The virus induces down regulation of NF-kB to liquidate the inhibitory activity for its replication triggered by the immune system leading a status of persistant HPV infection. During the progression to high grade intraepithelial neoplasia and cervical cancer NF-KB becomes constitutionally activated again. Mutations in NF-kB genes are rare in solid tumors but mutations of upstream signaling molecules such as RAS, EGFR, PGF, HER2 have been implicated in elevated NF-kB signaling. NF-kB can stimulate transcription of proliferation regulating genes (eg. cyclin D1 and c-myc), genes involved in metastasis, VEGF dependent angiogenesis and cell immortality by telomerase. NF-kB activation can also induce the expression of activation-induced cytodine deaminase (AID) and the APOBEC proteins, providing a mechanistic link between the NF-kB pathway and mutagenic characteristic of cervical cancer. Inhibition of NF-kB has the potential to be used to reverse resistance to radiotherapy and systemic anti-cancer medication, but currently no clinicaly active NF-kB targeting strategies are available.
http://ift.tt/2mFKyxv
Examining the bleeding incidences associated with targeted therapies used in metastatic renal cell carcinoma
Publication date: December 2017
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): MacKenzie Crist, Elizabeth Hansen, Lipika Chablani, Elizabeth Guancial
A systematic review was conducted to illustrate the bleeding risks associated with targeted therapies used in the treatment of metastatic renal cell carcinoma (mRCC). Eligible studies included phase II, III, or IV clinical trials using pazopanib, sunitinib, cabozantinib, lenvatinib, everolimus, temsirolimus, bevacizumab, axitinib, and/or sorafenib in the setting of mRCC. Types of bleeding event(s), bleeding event frequency, and incidence of thrombocytopenia were collected from the relevant articles. ClinicalTrials.gov was also searched for incidence of "Serious bleeding adverse effects" reported in these trials. The incidences of bleeding events ranged from 1 to 36%, and incidences of thrombocytopenia ranged from 2 to 78%. Available serious bleeding adverse events ranged from 1 to 7%. The highest percentage of bleeding incidences were seen with bevacizumab, while the lowest percentage of bleeding incidences were seen with axitinib. All of the included trials were of high quality per Jadad scoring.
http://ift.tt/2ypXL34
Impact of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) on cancer treatment outcomes: An overview about well-established and recently emerging clinical data
Publication date: December 2017
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Yassine Lalami, Jean Klastersky
Despite the overwhelming evidence for the role of granulocyte colony stimulating factors (G-CSF) in managing febrile neutropenia (FN) risk, chemotherapy-induced neutropenia (CIN) and/or FN still remain the most common reasons for reducing relative dose intensity (RDI) and/or delaying chemotherapy schedule. The need to maintain RDI to ensure optimal clinical outcomes is one of the key rationales for utilizing G-CSF. There is a high incidence of reduced RDI in both curative and palliative settings, and this observation is especially evidenced in retrospective analyses. Reduced RDI leads to significantly decreased survival outcomes and quality of life in various malignancies at various clinical settings and stages.Beyond its role as a surrogate prognostic marker, high-grade CIN may have an unexpected predictive role in clinical practice, as illustrated by several data relating CIN occurrence with favorable survival outcomes; this may be due to the fact that body surface area (BSA) – based calculation of dose may not fully account for the pharmacokinetics (PK) of cytotoxic drugs and the fact that there may be variability in drug metabolism between patients treated with same chemotherapy regimens.
http://ift.tt/2AvwYyU
Biomarkers in Prostate Cancer – Current Clinical Utility and Future Perspectives
Source:Critical Reviews in Oncology/Hematology
Author(s): Alexander Kretschmer, Derya Tilki
Current tendencies in the treatment course of prostate cancer patients increase the need for reliable biomarkers that help in decision-making in a challenging clinical setting. Within the last decade, several novel biomarkers have been introduced. In the following comprehensive review article, we focus on diagnostic (PHI®, 4K score, SelectMDx®, ConfirmMDx®, PCA3, MiPS, ExosomeDX, mpMRI) and prognostic (OncotypeDX GPS®, Prolaris®, ProMark®, DNA-ploidy, Decipher®) biomarkers that are in widespread clinical use and are supported by evidence. Hereby, we focus on multiple clinical situations in which innovative biomarkers may guide decision-making in prostate cancer therapy. In addition, we describe novel liquid biopsy approaches (circulating tumour cells, cell-free DNA) that have been described as predictive biomarkers in metastatic castration-resistant prostate cancer and might support an individual patient-centred oncological approach in the nearer future.
http://ift.tt/2hBP8Yc
Optimization and purification of l-asparaginase from fungi: A systematic review
Source:Critical Reviews in Oncology/Hematology
Author(s): Paula Monteiro Souza, Marcela Medeiros de Freitas, Samuel Leite Cardoso, Adalberto Pessoa, Eliete Neves Silva Guerra, Pérola Oliveira Magalhães
The purpose of this systematic review was to identify the available literature of the l-asparaginase producing fungi. This study followed the Preferred Reporting Items for Systematic Reviews. The search was conducted on five databases: LILACS, PubMed, Science Direct, Scopus and Web of Science up until July 20th, 2016, with no time or language restrictions. The reference list of the included studies was crosschecked and a partial gray literature search was undertaken. The methodology of the selected studies was evaluated using GRADE. Asparaginase production, optimization using statistical design, purification and characterization were the main evaluated outcomes. Of the 1,686 initially gathered studies, 19 met the inclusion criteria after a two-step selection process. Nine species of fungi were reported in the selected studies, out of which 13 studies optimized the medium composition using statistical design for enhanced asparaginase production and six reported purification and characterization of the enzyme. The genera Aspergillus were identified as producers of asparaginase in both solid and submerged fermentation and l-asparagine was the amino acid most used as nitrogen source. This systematic review demonstrated that different fungi produce l-asparaginase, which possesses a potential in leukemia treatment. However, further investigations are required to confirm the promising effect of these fungal enzymes.
http://ift.tt/2zPdgBa
Concomitant Use Of Corticosteroids And Immune Checkpoint Inhibitors In Patients With Hematologic Or Solid Neoplasms: A Systematic Review
Source:Critical Reviews in Oncology/Hematology
Author(s): A. Garant, C. Guilbault, T. Ekmekjian, Z. Greenwald, P. Murgoi, T. Vuong
PurposeClinical trials studying immune checkpoint inhibitors exclude patients on corticosteroids, due to the hypothesis that corticosteroids may antagonize immunotherapy. We performed a systematic review of the literature looking at the clinical outcomes of cancer patients treated with immune checkpoint inhibitors and concomitant corticosteroids.MethodsThe following databases were searched for relevant studies: MEDLINE, Embase Classic+Embase, BIOSIS Previews, the Cochrane Database of Systematic Reviews, the CENTRAL Registry of Controlled Trials, Web of Science and Scopus. Abstracts from the meetings of the European Cancer Congress/European Society for Medical Oncology, the American Society of Clinical Oncology, the American Society of Hematology, the European Society for Radiotherapy & Oncology, the American Society for Radiation Oncology and the European Society for Radiotherapy & Oncology were manually searched. Two independent reviewers screened the references: case reports and articles with a low risk of bias were retained.ResultsFollowing a retrieval of 14603 unique references, 140 abstracts were retained for review; 27 articles are in the final analysis. Although limited, the reviewed data suggests that the concomitant administration of corticosteroids and immune checkpoint inhibitors may not necessarily lead to poorer clinical outcomes.ConclusionIn our systematic review, there was no objective data on the exact types of corticosteroids and the dose threshold above which an interaction could be measured clinically. Consideration of stratified randomization and treatment sequence evaluations in prospective trials may clarify this challenging topic and perhaps improve patient access to immune checkpoint therapies.
http://ift.tt/2zP8XG4
The predictive value of primary tumor location in patients with metastatic colorectal cancer: A systematic review
Publication date: Available online 7 November 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Nele Boeckx, Katleen Janssens, Guy Van Camp, Marika Rasschaert, Konstantinos Papadimitriou, Marc Peeters, Ken Op de Beeck
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. It has been reported that left- and right-sided CRC harbor varying disease characteristics, which leads to a difference in prognosis and response to therapy. Recently, there have been retrospective studies about tumor location in metastatic CRC (mCRC) and its potential to predict the effect of anti-vascular endothelial growth factor and anti-epidermal growth factor receptor (anti-EGFR) therapies. In this review, we provide a comprehensive overview of the latest trials studying the predictive value of primary tumor location in mCRC and discuss biomarkers that might be associated with the differences in treatment response. Although data need to be interpreted with caution due to the absence of randomized trials stratified based on tumor location, patients with left-sided CRC seem to benefit more from anti-EGFR therapy than patients with right-sided CRC. Further clinical trials, stratified for tumor location, are warranted.
http://ift.tt/2hBOWbq
Ovarian sex-cord stromal tumours and small cell tumours: pathological, genetic and management aspects
Source:Critical Reviews in Oncology/Hematology
Author(s): Stergios Boussios, Michelle Moschetta, George Zarkavelis, Alexandra Papadaki, Aristides Kefas, Konstantina Tatsi
Non-epithelial ovarian cancers (NEOC) constitute a group of uncommon malignancies and their treatment is still a challenging task. Collectively, these tumours account for about 10% of all ovarian cancers and occur in all age groups from childhood to old-age. They include malignancies of germ cell origin, sex cord-stromal cell origin, and a variety of extremely rare ovarian cancers, such as small-cell carcinomas and sarcomas. Each of these classifications encompasses multiple histologic subtypes. It is imperative that these rare tumours are managed with accurate diagnosis, staging, and treatment, to optimise the outcome. The aetiology and molecular origins of each sub-group of NEOC remain largely unresolved, and international cooperation to promote high quality translational research is crucial. Much effort has been made into researching the molecular mechanisms underlying epithelial ovarian cancers, but far less is known about the genetic changes in NEOC. In this article, it is provided an overview of the current knowledge on the incidence, clinical presentation, pathology, genetics, therapeutic interventions, survival and prognostic factors of adult and juvenile granulosa cell tumours (GrCT), Sertoli-Leydig Cell tumours (SLCT) and small cell carcinoma of the ovary. We also consider future potential therapeutic targets in these rare cancers.
http://ift.tt/2yNCccu
Effects of exercise on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: A systematic review
Source:Critical Reviews in Oncology/Hematology
Author(s): Duregon Federica, Vendramin Barbara, Bullo Valentina, Gobbo Stefano, Cugusi Lucia, Di Blasio Andrea, Neunhaeuserer Daniel, Zaccaria Marco, Bergamin Marco, Ermolao Andrea
BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological and clinically relevant side effect of many commonly used chemotherapeutic agents. Moreover, little effort has been done to investigate the potentially beneficial effects of specific exercises to counteract the CIPN symptoms.ObjectiveThis document aims to summarize and analyze systematically the current body of evidence about the effects of specific exercise protocols on CIPN symptoms, balance control, physical function and quality of life in patients with CIPN.Literature surveySpecific terms were identified for the literature research in MEDLINE, Scopus, Bandolier, PEDro, and Web of Science.MethodologyFour manuscripts were considered eligible for this review. Quality appraisal distinguished two studies as high quality investigations while two with low quality. Results were summarized in the following domains: "CIPN symptoms", "Static balance control", "Dynamic balance control", "Quality of life and Physical function".SynthesisSignificant improvements were detected on postural control. Additionally, patients' quality of life and independence were found ameliorated after exercise sessions. Combined exercise protocols including endurance, strength and sensorimotor training showed larger improvements.ConclusionsThis systematic review comes from a highly selected but small source of data. Nevertheless, specific exercise for cancer patients undergoing chemotherapy with CIPN symptoms should be recommended since these interventions appeared as feasible and have been demonstrated as useful tools to counteract some of the limitations due to chemotherapy.
http://ift.tt/2hBOR7C
Editorial Board
Publication date: November 2017
Source:Critical Reviews in Oncology/Hematology, Volume 119
http://ift.tt/2zQFdsi
Erratum to “Systematic literature review of health-related quality of life in locally-advanced non-small cell lung cancer: Has it yet become state-of-the-art?” [Crit. Rev. Oncol. Hematol., 119 (November) (2017) 40–49]
Source:Critical Reviews in Oncology/Hematology
Author(s): Lotte van der Weijst, Veerle Surmont, Wim Schrauwen, Yolande Lievens
from Cancer via ola Kala on Inoreader http://ift.tt/2mFZ0pt
via IFTTT
Fertility management for malignant ovarian germ cell tumors patients
Publication date: December 2017
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Chiara Di Tucci, Assunta Casorelli, Elisa Morrocchi, Innocenza Palaia, Ludovico Muzii, Pierluigi Benedetti Panici
Malignant Germ Cell Tumors have primarily affecting adolescents and young adults. In advanced disease, greater than 70% of patients can be cured with standard chemotherapy regimens and fertility-sparing surgery appears to be safe with excellent survival after long-term follow-up.Due to their rarity, follow up and fertility management is largely based on trials of epithelial ovarian cancer or on few small studies.We report a review of the literature studies about the assessment, the monitoring and the treatment of fertility for Malignant Germ Cell Tumors as pratical guidelines for management of fertility in these patients.
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Management of salivary gland malignant tumor: The policlinico Umberto I, sapienza university of rome head and neck unit clinical recommendations
Publication date: Available online 27 October 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Francesca De Felice, Marco de incentiis, Valentino Valentini, Daniela Musio, Silvia Mezi, Luigi Lo Mele, Marco Della Monaca, Vittorio D'Aguanno, Valentina Terenzi, Martina Di Brino, Edoardo Brauner, Nadia Bulzonetti, Gianluca Tenore, Giulia Pomati, Andrea Cassoni, Mario Tombolini, Andrea Battisti, Antonio Greco, Giorgio Pompa, Antonio Minni, Umberto Romeo, Enrico Cortesi, Antonella Polimeni, Vincenzo Tombolini
Salivary gland malignant tumor (SGMT) is a malignant disease requiring multidisciplinary approach. The rare incidence and the consequent lack of robust evidence-based medicine has called for a comprehensive update to draw recommendations for clinical practice. This paper is a summary of the XXX Head and Neck Unit guidelines regarding the management of SGMT. Recommendations include the indications for exclusive and adjuvant therapy, as well as metastatic management, for both major and minor SGMT.
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Incidence of skin toxicity in squamous cell carcinoma of the head and neck treated with radiotherapy and cetuximab: A systematic review
Publication date: December 2017
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Pierluigi Bonomo, Mauro Loi, Isacco Desideri, Emanuela Olmetto, Camilla Delli Paoli, Francesca Terziani, Daniela Greto, Monica Mangoni, Silvia Scoccianti, Gabriele Simontacchi, Giulio Francolini, Icro Meattini, Saverio Caini, Lorenzo Livi
PurposeRadiotherapy plus cetuximab is an effective combination therapy for locally advanced head and neck squamous cell carcinoma. The aim of our study was to determine the frequency of skin toxicity in patients receiving the combined treatment.ResultsForty-eight studies were included in our analysis, for a total of 2152 patients. The mean rates of G3/G4 radiation dermatitis and acneiform rash were 32.5% (SD: 20.4; 95% CI: 28.5–36.5) and 13.4% (SD: 11.5; 95% CI: 11.2–15.6), respectively. The majority of studies referred to CTCAE scales for reporting both side effects (85.7% and 92.1%, respectively). Data on the management of skin toxicity were available in only 35.4% of the reviewed literature.Conclusionssevere radiation dermatitis is a frequent side effect induced by the combination of radiotherapy and cetuximab in head and neck cancer. The lack of predictive biomarkers of toxicity hampers the possibilty to design preventive measures on a personalized basis.
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The effects of enzalutamide and abiraterone on skeletal related events and bone radiological progression free survival in castration resistant prostate cancer patients: An indirect comparison of randomized controlled trials
Publication date: Available online 16 October 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Sergio Rizzo, Antonio Galvano, Francesco Pantano, Michele Iuliani, Bruno Vincenzi, Francesco Passiglia, Silvia Spoto, Giuseppe Tonini, Viviana Bazan, Antonio Russo, Daniele Santini
Two new drugs, the CYP17 inhibitor abiraterone acetate and the androgen receptor (AR) antagonist enzalutamide, have recently shown to prolong OS prior chemotherapy or in docetaxel treated mCRPC patients, using steroidal therapy or placebo as control group. Updated analyses underlined the role of these new agents on two prostate-specific endpoints as radiographic progression-free survival (rPFS) and time to first skeletal-related event (tSRE). On the basis of these reports, we made an indirect comparison between abiraterone and enzalutamide. We obtained a clinically but not significant difference favouring enzalutamide over abiraterone in terms of rPFS (HR 0.48, 95% CI 0.22–1.02). No significant difference was shown in term of tSRE (HR 0.99, 95% CI 0.83–1.17). In conclusion, abiraterone and enzalutamide have both demonstrated to significantly delay the bone progression resulting in similar improvements in bone-related endpoints in patients with mCRPC.
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Developing chemotherapy for diffuse pontine intrinsic gliomas (DIPG)
Publication date: December 2017
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Ho-Shin Gwak, Hyeon Jin Park
Prognosis of diffuse intrinsic pontine glioma (DIPG) is poor, with a median survival of 10 months after radiation. At present, chemotherapy has failed to show benefits over radiation.Advances in biotechnology have enabled the use of autopsy specimens for genomic analyses and molecular profiling of DIPG, which are quite different from those of supratentorial high grade glioma. Recently, combined treatments of cytotoxic agents with target inhibitors, based on biopsied tissue, are being examined in on-going trials. Spontaneous DIPG mice models have been recently developed that is useful for preclinical studies. Finally, the convection-enhanced delivery could be used to infuse drugs directly into the brainstem parenchyma, to which conventional systemic administration fails to achieve effective concentration.The WHO glioma classification defines a diffuse midline glioma with a H3-K27M-mutation, and we expect increase of tissue confirmation of DIPG, which will give us the biological information helping the development of a targeted therapy.
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ERCC1 as a prognostic factor for survival in patients with advanced urothelial cancer treated with platinum based chemotherapy: A systematic review and meta-analysis
Publication date: December 2017
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Yuksel Urun, Jeffrey J. Leow, Andre P. Fay, Laurence Albiges, Toni K. Choueiri, Joaquim Bellmunt
BackgroundThe predictive role of excision repair cross-complementing group 1 (ERCC1) as a predictive factor in patients with advanced urothelial cancer (AUC) treated with platinum-based treatment is not well defined. Here, we evaluate the role of ERCC1 in patients with AUC treated with platinum-based treatment.MethodsWe performed comprehensive, systematic computerized search to identify relevant studies through Medline, Embase, Cochrane Controlled Trials Register (CCTR) databases and abstracts from American Society of Clinical Oncology (ASCO) and ASCO Genitourinary Cancers Symposium, European Society For Medical Oncology (ESMO) and European Association of Urology (EAU) meeting up to July 2015. A systematic review and meta-analysis were performed.ResultsWe included a total of 1475 patients from 13 studies. We found that ERCC1 positivity was significantly associated with worse progression-free survival (pooled HR: 1.54, 95% CI: 1.13–2.11, p=0.006). There was no significant association with overall survival (pooled HR1.63, 95% CI: 0.93–2.88, p=0.09) and disease-free survival (pooled HR: 1.092, 95% CI: 0.63–1.90, p=0.75).ConclusionERCC1 positivity might be a prognostic indicator for poorer survival outcomes among patients with AUC. ERCC1 positivity was trending to poorer OS but was statistically worse for PFS. Further large prospective studies are warranted as ERCC1 could be used as a predictive marker to direct treatment of patients with AUC.
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The role of Nuclear Factor-kappa B signaling in human cervical cancer
Publication date: December 2017
Source:Critical Reviews in Oncology/Hematology, Volume 120
Author(s): Sam Tilborghs, Jerome Corthouts, Yannick Verhoeven, David Arias, Christian Rolfo, Xuan Bich Trinh, Peter A. van Dam
Background The Nuclear Factor kappaB (NF-kB) family consists of transcription factors that play a complex and essential role in the regulation of immune responses and inflammation. NF-kB has recently generated considerable interest as it has been implicated in human cancer initiation, progression and resistance to treatment. In the present comprehensive review the different aspects of NF-kB signaling in the carcinogenesis of cancer of the uterine cervix are discussed. NF-kB functions as part of a network, which determines the pattern of its effects on the expression of several other genes (such as crosstalks with reactive oxygen species, p53, STAT3 and miRNAS) and thus its function. Activation of NF-kB triggered by a HPV infection is playing an important role in the innate and adaptive immune response of the host. The virus induces down regulation of NF-kB to liquidate the inhibitory activity for its replication triggered by the immune system leading a status of persistant HPV infection. During the progression to high grade intraepithelial neoplasia and cervical cancer NF-KB becomes constitutionally activated again. Mutations in NF-kB genes are rare in solid tumors but mutations of upstream signaling molecules such as RAS, EGFR, PGF, HER2 have been implicated in elevated NF-kB signaling. NF-kB can stimulate transcription of proliferation regulating genes (eg. cyclin D1 and c-myc), genes involved in metastasis, VEGF dependent angiogenesis and cell immortality by telomerase. NF-kB activation can also induce the expression of activation-induced cytodine deaminase (AID) and the APOBEC proteins, providing a mechanistic link between the NF-kB pathway and mutagenic characteristic of cervical cancer. Inhibition of NF-kB has the potential to be used to reverse resistance to radiotherapy and systemic anti-cancer medication, but currently no clinicaly active NF-kB targeting strategies are available.
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Downregulation of DUSP4 enhances cell proliferation and invasiveness in colorectal carcinomas
Abstract
It is widely accepted that aberrant activation of the Wnt signaling pathway is responsible for the development of precursor lesions of colorectal cancer (CRC). However, the molecular mechanisms involved in the process of progression from these precursor lesions to invasive lesions of CRC are not fully understood. Recently, we reported that constitutive activation of MAPK accompanied by downregulation of dual-specificity phosphatase 4 (DUSP4), a MAPK phosphatase, contributes to the progression of precursor lesions in the pancreas. In this study, we found that downregulation of DUSP4 was related to constitutive activation of extracellular signal-regulated kinases (ERKs) in CRC cells. Restoration of DUSP4 resulted in inactivation of ERKs, leading to suppression of both proliferation and invasiveness, as shown by treatment with a MEK inhibitor. Furthermore, immunohistochemistry revealed that DUSP4 expression was upregulated in the superficial region of CRC tissue, whereas it was significantly downregulated in the deep region. On the other hand, ERKs in the deep region were markedly hyper-activated compared to those in the superficial region. These results suggest that activation of the MAPK signaling pathway caused by downregulation of DUSP4 is responsible for progression of CRCs and would be a promising therapeutic target.
This article is protected by copyright. All rights reserved.
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Downregulation of DUSP4 enhances cell proliferation and invasiveness in colorectal carcinomas
Abstract
It is widely accepted that aberrant activation of the Wnt signaling pathway is responsible for the development of precursor lesions of colorectal cancer (CRC). However, the molecular mechanisms involved in the process of progression from these precursor lesions to invasive lesions of CRC are not fully understood. Recently, we reported that constitutive activation of MAPK accompanied by downregulation of dual-specificity phosphatase 4 (DUSP4), a MAPK phosphatase, contributes to the progression of precursor lesions in the pancreas. In this study, we found that downregulation of DUSP4 was related to constitutive activation of extracellular signal-regulated kinases (ERKs) in CRC cells. Restoration of DUSP4 resulted in inactivation of ERKs, leading to suppression of both proliferation and invasiveness, as shown by treatment with a MEK inhibitor. Furthermore, immunohistochemistry revealed that DUSP4 expression was upregulated in the superficial region of CRC tissue, whereas it was significantly downregulated in the deep region. On the other hand, ERKs in the deep region were markedly hyper-activated compared to those in the superficial region. These results suggest that activation of the MAPK signaling pathway caused by downregulation of DUSP4 is responsible for progression of CRCs and would be a promising therapeutic target.
This article is protected by copyright. All rights reserved.
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Thyroid Cancer: Is It All in the Genes?
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BRAF V600E Mutation-Assisted Risk Stratification of Solitary Intrathyroidal Papillary Thyroid Cancer for Precision Treatment
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Investigation of the Relationship Between Radiation Dose and Gene Mutations and Fusions in Post-Chernobyl Thyroid Cancer
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MR imaging perfusion and diffusion analysis to assess preoperative Short Course Radiotherapy response in locally advanced rectal cancer: Standardized Index of Shape by DCE-MRI and intravoxel incoherent motion-derived parameters by DW-MRI
Abstract
Our aim is to assess preoperative Short Course Radiotherapy (SCR) tumor response in locally advanced rectal cancer (LARC) through Standardized Index of Shape (SIS) by DCE-MRI, apparent diffusion coefficient (ADC) and intravoxel incoherent motion-derived parameters by DW-MRI. 35 patients with LARC underwent MR scan before and after SCR followed by delayed surgery, retrospectively, were enrolled. SIS, ADC, tissue diffusion (D t), pseudodiffusion (D p), and perfusion fraction (f) were extracted by MRI for each patient before and after SCR. Tumor regression grade (TRG) was estimated. Receiver operating characteristic curve and linear classification were performed. Sixteen patients were classified as responders (TRG ≤ 2) and 19 as non-responders. Seven patients had TRG1 [pathological complete response (pCR)]. The best parameter to discriminate responders by non-responders was SIS (sensitivity 94%, specificity 84%, accuracy 89%, cutoff value = − 7.8%). SIS obtained the best diagnostic performance also to discriminate pCR (sensitivity 86%, specificity 89%, accuracy 89%, cutoff value = 68.2%). No accuracy increase was obtained combining linearly each possible parameters couple or all functional MR-derived parameters. SIS is a hopeful DCE-MRI angiogenic biomarker to assess preoperative treatment response after SCR with delayed surgery, and it permits to discriminate pCR allowing to direct surgery for tailored and conservative treatment.
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MR imaging perfusion and diffusion analysis to assess preoperative Short Course Radiotherapy response in locally advanced rectal cancer: Standardized Index of Shape by DCE-MRI and intravoxel incoherent motion-derived parameters by DW-MRI
Abstract
Our aim is to assess preoperative Short Course Radiotherapy (SCR) tumor response in locally advanced rectal cancer (LARC) through Standardized Index of Shape (SIS) by DCE-MRI, apparent diffusion coefficient (ADC) and intravoxel incoherent motion-derived parameters by DW-MRI. 35 patients with LARC underwent MR scan before and after SCR followed by delayed surgery, retrospectively, were enrolled. SIS, ADC, tissue diffusion (D t), pseudodiffusion (D p), and perfusion fraction (f) were extracted by MRI for each patient before and after SCR. Tumor regression grade (TRG) was estimated. Receiver operating characteristic curve and linear classification were performed. Sixteen patients were classified as responders (TRG ≤ 2) and 19 as non-responders. Seven patients had TRG1 [pathological complete response (pCR)]. The best parameter to discriminate responders by non-responders was SIS (sensitivity 94%, specificity 84%, accuracy 89%, cutoff value = − 7.8%). SIS obtained the best diagnostic performance also to discriminate pCR (sensitivity 86%, specificity 89%, accuracy 89%, cutoff value = 68.2%). No accuracy increase was obtained combining linearly each possible parameters couple or all functional MR-derived parameters. SIS is a hopeful DCE-MRI angiogenic biomarker to assess preoperative treatment response after SCR with delayed surgery, and it permits to discriminate pCR allowing to direct surgery for tailored and conservative treatment.
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Significance of prostate-specific antigen kinetics after three-dimensional conformal radiotherapy with androgen deprivation therapy in patients with localized prostate cancer
Abstract
Background
To evaluate the relationship between biochemical recurrence and post-radiation prostate-specific antigen (PSA) kinetics in patients with localized prostate cancer treated by radiotherapy with various durations of androgen deprivation therapy (ADT).
Methods
We reviewed our single-institution, retrospectively maintained data of 144 patients with T1c-T3N0M0 prostate cancer who underwent three-dimensional conformal radiotherapy (3D-CRT) between December 2005 and December 2015 and 113 patients were fulfilled the inclusion criteria. In this cohort, 3D-CRT was delivered with a dose in the range from 70.0 to 72.0 Gy with ADT. All patients received ADT as concurrent regimens. Biochemical recurrence was defined on the basis of the following: "PSA nadir + 2.0 ng/ml or the clinical judgement of attending physicians". Kaplan–Meier, log-rank, and Cox regression analyses were carried out.
Results
The median follow-up period was 54.0 months. The median duration of ADT was 17 months (interquartile range, 10–24 months). There was a trend toward statistical significant correlation between post-radiation PSA decline rate of ≥ 90% and PSA recurrence (p = 0.056). The same correlation could be observed in D'Amico high-risk patients (p = 0.036). However, it was not observed between PSA nadir and PSA recurrence (p = 0.40) in univariate analysis. Furthermore, multivariate analysis showed that post-radiation PSA decline rate of ≥ 90% was a significant predictor of biochemical recurrence in patients who received radiotherapy with various durations of ADT (p = 0.044).
Conclusions
Post-radiation PSA decline rate of ≥ 90% was a prognostic factor for biochemical recurrence in localized prostate cancer patients received 3D-CRT with various durations of ADT.
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Significance of prostate-specific antigen kinetics after three-dimensional conformal radiotherapy with androgen deprivation therapy in patients with localized prostate cancer
Abstract
Background
To evaluate the relationship between biochemical recurrence and post-radiation prostate-specific antigen (PSA) kinetics in patients with localized prostate cancer treated by radiotherapy with various durations of androgen deprivation therapy (ADT).
Methods
We reviewed our single-institution, retrospectively maintained data of 144 patients with T1c-T3N0M0 prostate cancer who underwent three-dimensional conformal radiotherapy (3D-CRT) between December 2005 and December 2015 and 113 patients were fulfilled the inclusion criteria. In this cohort, 3D-CRT was delivered with a dose in the range from 70.0 to 72.0 Gy with ADT. All patients received ADT as concurrent regimens. Biochemical recurrence was defined on the basis of the following: "PSA nadir + 2.0 ng/ml or the clinical judgement of attending physicians". Kaplan–Meier, log-rank, and Cox regression analyses were carried out.
Results
The median follow-up period was 54.0 months. The median duration of ADT was 17 months (interquartile range, 10–24 months). There was a trend toward statistical significant correlation between post-radiation PSA decline rate of ≥ 90% and PSA recurrence (p = 0.056). The same correlation could be observed in D'Amico high-risk patients (p = 0.036). However, it was not observed between PSA nadir and PSA recurrence (p = 0.40) in univariate analysis. Furthermore, multivariate analysis showed that post-radiation PSA decline rate of ≥ 90% was a significant predictor of biochemical recurrence in patients who received radiotherapy with various durations of ADT (p = 0.044).
Conclusions
Post-radiation PSA decline rate of ≥ 90% was a prognostic factor for biochemical recurrence in localized prostate cancer patients received 3D-CRT with various durations of ADT.
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A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy.
| Related Articles |
A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy.
Cancer Biol Ther. 2017 Nov 16;:1-8
Authors: Yang M, Yang CS, Guo W, Tang J, Huang Q, Feng S, Jiang A, Xu X, Jiang G, Liu YQ
Abstract
Significant progress has been made in the diagnosis and treatment of cancer; however, significant challenges remain. Conditionally replicating adenoviruses (CRAds), which not only kill cancer cells, but also serve as vectors to express therapeutic genes, are a novel and effective method to treat cancer. However, most adenoviruses are Ad5, which infect cells through the coxsackie and adenovirus receptor (CAR). The transduction efficacy of Ad5 is restricted because of the absent or low expression of CAR on several cancer cells. Ad serotype 35 has a different tropism pattern to Ad5. Ad35 attaches to cells via a non-CAR receptor, CD46, which is expressed widely on most tumor cells. Thus, chimeric adenoviral vectors consisting of the knob and shaft of Ad35 combined with Ad5 have been constructed. The chimeric fiber adenoviral vectors can transduce CAR-positive and CAR-negative cell lines. In this review, we explore the application of the novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 in tumor therapy in terms of safety, mechanism, transduction efficacy, and antitumor effect.
PMID: 29144842 [PubMed - as supplied by publisher]
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A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy.
| Related Articles |
A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy.
Cancer Biol Ther. 2017 Nov 16;:1-8
Authors: Yang M, Yang CS, Guo W, Tang J, Huang Q, Feng S, Jiang A, Xu X, Jiang G, Liu YQ
Abstract
Significant progress has been made in the diagnosis and treatment of cancer; however, significant challenges remain. Conditionally replicating adenoviruses (CRAds), which not only kill cancer cells, but also serve as vectors to express therapeutic genes, are a novel and effective method to treat cancer. However, most adenoviruses are Ad5, which infect cells through the coxsackie and adenovirus receptor (CAR). The transduction efficacy of Ad5 is restricted because of the absent or low expression of CAR on several cancer cells. Ad serotype 35 has a different tropism pattern to Ad5. Ad35 attaches to cells via a non-CAR receptor, CD46, which is expressed widely on most tumor cells. Thus, chimeric adenoviral vectors consisting of the knob and shaft of Ad35 combined with Ad5 have been constructed. The chimeric fiber adenoviral vectors can transduce CAR-positive and CAR-negative cell lines. In this review, we explore the application of the novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 in tumor therapy in terms of safety, mechanism, transduction efficacy, and antitumor effect.
PMID: 29144842 [PubMed - as supplied by publisher]
http://ift.tt/2yTWRIl
A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy.
| Related Articles |
A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy.
Cancer Biol Ther. 2017 Nov 16;:1-8
Authors: Yang M, Yang CS, Guo W, Tang J, Huang Q, Feng S, Jiang A, Xu X, Jiang G, Liu YQ
Abstract
Significant progress has been made in the diagnosis and treatment of cancer; however, significant challenges remain. Conditionally replicating adenoviruses (CRAds), which not only kill cancer cells, but also serve as vectors to express therapeutic genes, are a novel and effective method to treat cancer. However, most adenoviruses are Ad5, which infect cells through the coxsackie and adenovirus receptor (CAR). The transduction efficacy of Ad5 is restricted because of the absent or low expression of CAR on several cancer cells. Ad serotype 35 has a different tropism pattern to Ad5. Ad35 attaches to cells via a non-CAR receptor, CD46, which is expressed widely on most tumor cells. Thus, chimeric adenoviral vectors consisting of the knob and shaft of Ad35 combined with Ad5 have been constructed. The chimeric fiber adenoviral vectors can transduce CAR-positive and CAR-negative cell lines. In this review, we explore the application of the novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 in tumor therapy in terms of safety, mechanism, transduction efficacy, and antitumor effect.
PMID: 29144842 [PubMed - as supplied by publisher]
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Resveratrol Induces Mitochondrial Apoptosis and Inhibits Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma Cells.
Resveratrol Induces Mitochondrial Apoptosis and Inhibits Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma Cells.
Nutr Cancer. 2017 Nov 17;:1-11
Authors: Kim SE, Shin SH, Lee JY, Kim CH, Chung IK, Kang HM, Park HR, Park BS, Kim IR
Abstract
OSCC is the most common malignant cancer of the head and neck. EMT is an essential cellular process critical to the morphogenesis and homeostasis of solid tissues. It is also involved in the initial stage of cancer metastasis and invasion in which cells lose epithelial characteristics. While cancer therapy protocols such as surgery, radiation, and chemotherapy are effective and useful, the drug tolerance and toxicity of OSCC patients remain a problem. Resveratrol is mainly produced in red grape skin and exhibits anti-oxidative, anti-inflammatory, anti-proliferative, and anti-cancer properties. This study was undertaken to investigate the underlying mechanisms giving rise to the induction of apoptosis by resveratrol in the human tongue squamous cell carcinoma cell line. Resveratrol treatment resulted in a time- and dose-dependent decrease in cell viability and increased the apoptotic cell ratio in CAL-27, SCC15, and SCC25 cells. Resveratrol treatment of CAL-27 cells showed that several lines of apoptotic manifestation and decreased cell migration, invasion, and EMT-inducing transcription factor. Taken together, our findings demonstrate the inhibitory effect of resveratrol in human OSCC cells via the mitochondrial pathway and that resveratrol is able to inhibit cell invasion and migration by inhibiting the EMT-inducing transcription factors.
PMID: 29148840 [PubMed - as supplied by publisher]
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Resveratrol Induces Mitochondrial Apoptosis and Inhibits Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma Cells.
Resveratrol Induces Mitochondrial Apoptosis and Inhibits Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma Cells.
Nutr Cancer. 2017 Nov 17;:1-11
Authors: Kim SE, Shin SH, Lee JY, Kim CH, Chung IK, Kang HM, Park HR, Park BS, Kim IR
Abstract
OSCC is the most common malignant cancer of the head and neck. EMT is an essential cellular process critical to the morphogenesis and homeostasis of solid tissues. It is also involved in the initial stage of cancer metastasis and invasion in which cells lose epithelial characteristics. While cancer therapy protocols such as surgery, radiation, and chemotherapy are effective and useful, the drug tolerance and toxicity of OSCC patients remain a problem. Resveratrol is mainly produced in red grape skin and exhibits anti-oxidative, anti-inflammatory, anti-proliferative, and anti-cancer properties. This study was undertaken to investigate the underlying mechanisms giving rise to the induction of apoptosis by resveratrol in the human tongue squamous cell carcinoma cell line. Resveratrol treatment resulted in a time- and dose-dependent decrease in cell viability and increased the apoptotic cell ratio in CAL-27, SCC15, and SCC25 cells. Resveratrol treatment of CAL-27 cells showed that several lines of apoptotic manifestation and decreased cell migration, invasion, and EMT-inducing transcription factor. Taken together, our findings demonstrate the inhibitory effect of resveratrol in human OSCC cells via the mitochondrial pathway and that resveratrol is able to inhibit cell invasion and migration by inhibiting the EMT-inducing transcription factors.
PMID: 29148840 [PubMed - as supplied by publisher]
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The roles of vasohibin and its family members: Beyond angiogenesis modulators
.
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Deactivation of cisplatin-resistant human lung/ovary cancer cells with pyropheophorbide-α methyl ester-photodynamic therapy
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LncRNA CCAT1/miR-130a-3p axis increases cisplatin resistance in non-small-cell lung cancer cell line by targeting SOX4
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The roles of vasohibin and its family members: Beyond angiogenesis modulators
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The IGF-1R/AKT pathway has opposing effects on Nutlin-3a-induced apoptosis
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A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy.
A novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 for tumor therapy.
Cancer Biol Ther. 2017 Nov 16;:1-8
Authors: Yang M, Yang CS, Guo W, Tang J, Huang Q, Feng S, Jiang A, Xu X, Jiang G, Liu YQ
Abstract
Significant progress has been made in the diagnosis and treatment of cancer; however, significant challenges remain. Conditionally replicating adenoviruses (CRAds), which not only kill cancer cells, but also serve as vectors to express therapeutic genes, are a novel and effective method to treat cancer. However, most adenoviruses are Ad5, which infect cells through the coxsackie and adenovirus receptor (CAR). The transduction efficacy of Ad5 is restricted because of the absent or low expression of CAR on several cancer cells. Ad serotype 35 has a different tropism pattern to Ad5. Ad35 attaches to cells via a non-CAR receptor, CD46, which is expressed widely on most tumor cells. Thus, chimeric adenoviral vectors consisting of the knob and shaft of Ad35 combined with Ad5 have been constructed. The chimeric fiber adenoviral vectors can transduce CAR-positive and CAR-negative cell lines. In this review, we explore the application of the novel fiber chimeric conditionally replicative adenovirus-Ad5/F35 in tumor therapy in terms of safety, mechanism, transduction efficacy, and antitumor effect.
PMID: 29144842 [PubMed - as supplied by publisher]
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Retracted: Silencing of the COPS3 Gene by siRNA Reduces Proliferation of Lung Cancer Cells Most Likely via Induction of Cell Cycle Arrest and Apoptosis
Retracted: Silencing of the COPS3 Gene by siRNA Reduces Proliferation of Lung Cancer Cells Most Likely via Induction of Cell Cycle Arrest and Apoptosis
Asian Pac J Cancer Prev. 2017 11 17;18(10):2893-2893
Authors:
Abstract
Retraction: Retracted: siRNA mediated silencing of NIN1/RPN12 binding protein 1 homolog inhibits proliferation and growth of breast cancer cells Asian Pacific Journal of Cancer Prevention has retracted the article titled "siRNA mediated silencing of NIN1/RPN12 binding protein 1 homolog inhibits proliferation and growth of breast cancer cells"(1) for reason of similarity with a series of articles identified by Byrne and Labbé (2). 1. Huang WY1, Chen DH, Ning L, Wang LW. siRNA mediated silencing of NIN1/RPN12 binding protein 1 homolog inhibits proliferation and growth of breast cancer cells. Asian Pac J Cancer Prev. 2012;13(5):1823-7. 2. J. A. Byrne and C. Labbé, "Striking similarities between publications from China describing single gene knockdown experiments in human cancer cell lines," Scientometrics, vol. 110, no. 3, pp. 1471–1493, 2017. Authors did not respond to request for comment.
PMID: 29148631 [PubMed - as supplied by publisher]
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Metformin as a repurposed therapy in advanced non-small cell lung cancer (NSCLC): results of a phase II trial
Summary
Background Metformin has been shown to have anti-neoplastic activity in non-small cell lung cancer (NSCLC) in both preclinical and observational studies, however this has never been prospectively evaluated. This single-arm phase II trial, while not fully accrued, is the first known prospective study evaluating the use of metformin with chemotherapy in advanced NSCLC. Methods Patients received carboplatin AUC 5 + pemetrexed 500 mg/m2 IV every 21 days for 4 cycles. For patients who achieved at least stable disease, maintenance pemetrexed was administered until progression or toxicity. Metformin was initiated at 1000 mg/day for week 1, 1500 mg/day for week 2, then 2000 mg/day thereafter, in divided doses. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and adverse events (AE). Tumor tissue was tested for LKB1/STK11 mutations, and non-fasting serum insulin levels were longitudinally assessed. Results Of a planned 50 patients, 14 were enrolled. ORR was 23% and median PFS was 3.9 months. Median OS was 11.7 months. No LKB1/STK11 mutations were identified. The most common AE were fatigue (42.9%), anemia, and nausea (28.6% each). The most common grade III AE was nausea (14.3%). No grade IV AE occurred. Mean duration of metformin treatment was 5.6 months. Conclusion Adding metformin to chemotherapy for advanced NSCLC was safe but did not significantly improve clinical outcomes compared to historical phase III controls. These results are limited by the small sample size; larger trials are needed.
http://ift.tt/2wEwGbJ
Mechanisms of cancer cell killing by sea cucumber-derived compounds
Summary
The aim of cancer therapy is to specifically eradicate tumor cells while causing minimal damage to normal tissues and minimal side-effects. Because of this, the use of natural substances with low toxicity is a good option. Sea cucumbers are one of many potential marine animals that contain valuable nutrients and medicinal properties. The medicinal value of sea cucumbers is attributed to the presence of bioactive agents with promising biological and pharmacological properties that include cytotoxic activity, induction of apoptosis, cell cycle arrest, inhibition of tumor growth, anti-metastatic and anti-angiogenic properties, and inhibition of drug resistance. This review discusses the mechanisms of cancer cell death induced by sea cucumber-derived compounds with regard to exploring the potential use of these marine natural products for cancer therapy.
http://ift.tt/2x9Brqv
Treatment-related serious adverse events and fatal adverse events with regorafenib in cancer patients: a meta-analysis of phase 3 randomized controlled trials
Summary
Regorafenib (Stivarga) is an oral small-molecule multikinase inhibitor commonly used against a variety of cancers. We performed a meta-analysis of all phase 3 randomized controlled trials (RCTs) of regorafenib to quantify the increased risk of SAEs and FAEs. We carried out a systematic search of electronic databases for studies published from inception to February 2017 without any restrictions. Eligibility criteria included phase 3 RCTs of tumors comparing regorafenib, alone or in combination with non-targeted chemotherapy (regorafenib arm) versus placebo or non-targeted chemotherapy (control arm). Data on SAEs and FAEs were extracted from each study and pooled to determine the overall incidence, relative risks (RRs) and 95% confidence intervals (CIs). A total of four phase 3 RCTs involving 1736 cancer patients met the eligibility criteria and were included. The overall incidence of SAEs and FAEs with regorafenib were 0.23 (95%CI, 0.05–0.40) and 0.02 (95%CI, 0.01–0.03), respectively. Compared with control, the summary RR of developing a regorafenib-related SAE was 1.60 (95%CI, 0.95–2.68, P=0.07), the summary RR of developing a regorafenib-related FAE was 1.71 (95%CI, 0.69–4.24, P=0.25). No evidence was found for the association between regorafenib and higher risk of SAEs and FAEs. This association varied significantly with cancer types (P=0.02) for SAEs but no evidence of heterogeneity was found for FAEs. This meta-analysis demonstrates no evidence for the association between regorafenib and higher risk of SAEs and FAEs. This analysis will be important when considering the trade-off of regorafenib treatment during clinical decision-making.
http://ift.tt/2flwSFd
Metformin as a repurposed therapy in advanced non-small cell lung cancer (NSCLC): results of a phase II trial
Summary
Background Metformin has been shown to have anti-neoplastic activity in non-small cell lung cancer (NSCLC) in both preclinical and observational studies, however this has never been prospectively evaluated. This single-arm phase II trial, while not fully accrued, is the first known prospective study evaluating the use of metformin with chemotherapy in advanced NSCLC. Methods Patients received carboplatin AUC 5 + pemetrexed 500 mg/m2 IV every 21 days for 4 cycles. For patients who achieved at least stable disease, maintenance pemetrexed was administered until progression or toxicity. Metformin was initiated at 1000 mg/day for week 1, 1500 mg/day for week 2, then 2000 mg/day thereafter, in divided doses. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and adverse events (AE). Tumor tissue was tested for LKB1/STK11 mutations, and non-fasting serum insulin levels were longitudinally assessed. Results Of a planned 50 patients, 14 were enrolled. ORR was 23% and median PFS was 3.9 months. Median OS was 11.7 months. No LKB1/STK11 mutations were identified. The most common AE were fatigue (42.9%), anemia, and nausea (28.6% each). The most common grade III AE was nausea (14.3%). No grade IV AE occurred. Mean duration of metformin treatment was 5.6 months. Conclusion Adding metformin to chemotherapy for advanced NSCLC was safe but did not significantly improve clinical outcomes compared to historical phase III controls. These results are limited by the small sample size; larger trials are needed.
from Cancer via ola Kala on Inoreader http://ift.tt/2wEwGbJ
via IFTTT
Mechanisms of cancer cell killing by sea cucumber-derived compounds
Summary
The aim of cancer therapy is to specifically eradicate tumor cells while causing minimal damage to normal tissues and minimal side-effects. Because of this, the use of natural substances with low toxicity is a good option. Sea cucumbers are one of many potential marine animals that contain valuable nutrients and medicinal properties. The medicinal value of sea cucumbers is attributed to the presence of bioactive agents with promising biological and pharmacological properties that include cytotoxic activity, induction of apoptosis, cell cycle arrest, inhibition of tumor growth, anti-metastatic and anti-angiogenic properties, and inhibition of drug resistance. This review discusses the mechanisms of cancer cell death induced by sea cucumber-derived compounds with regard to exploring the potential use of these marine natural products for cancer therapy.
from Cancer via ola Kala on Inoreader http://ift.tt/2x9Brqv
via IFTTT
Treatment-related serious adverse events and fatal adverse events with regorafenib in cancer patients: a meta-analysis of phase 3 randomized controlled trials
Summary
Regorafenib (Stivarga) is an oral small-molecule multikinase inhibitor commonly used against a variety of cancers. We performed a meta-analysis of all phase 3 randomized controlled trials (RCTs) of regorafenib to quantify the increased risk of SAEs and FAEs. We carried out a systematic search of electronic databases for studies published from inception to February 2017 without any restrictions. Eligibility criteria included phase 3 RCTs of tumors comparing regorafenib, alone or in combination with non-targeted chemotherapy (regorafenib arm) versus placebo or non-targeted chemotherapy (control arm). Data on SAEs and FAEs were extracted from each study and pooled to determine the overall incidence, relative risks (RRs) and 95% confidence intervals (CIs). A total of four phase 3 RCTs involving 1736 cancer patients met the eligibility criteria and were included. The overall incidence of SAEs and FAEs with regorafenib were 0.23 (95%CI, 0.05–0.40) and 0.02 (95%CI, 0.01–0.03), respectively. Compared with control, the summary RR of developing a regorafenib-related SAE was 1.60 (95%CI, 0.95–2.68, P=0.07), the summary RR of developing a regorafenib-related FAE was 1.71 (95%CI, 0.69–4.24, P=0.25). No evidence was found for the association between regorafenib and higher risk of SAEs and FAEs. This association varied significantly with cancer types (P=0.02) for SAEs but no evidence of heterogeneity was found for FAEs. This meta-analysis demonstrates no evidence for the association between regorafenib and higher risk of SAEs and FAEs. This analysis will be important when considering the trade-off of regorafenib treatment during clinical decision-making.
from Cancer via ola Kala on Inoreader http://ift.tt/2flwSFd
via IFTTT