PeerJ Preprints: Oncologyhttps://peerj.com/preprints/index.atom?journal=peerj&subject=5700Oncology articles published in PeerJ PreprintsMultifaceted role of tensins in cancerhttps://peerj.com/preprints/279902019-09-272019-09-27Abdulaziz AlfahedTeresa P RaposoMohammad Ilyas
Tensins are structural adaptor proteins localized at focal adhesions. Tensins can act as mechanosensors and participate in the transduction of biochemical signals from the extracellular matrix to the cytoskeleton, acting as an interface able to alter cell behavior in responses to changes in their surrounding environment. This review aims to provide a concise summary of the main functions of the four known tensins in cell and cancer biology, their homology and recently unveiled signaling mechanisms. We focus specifically on how tensin 4 (TNS4/Cten) may contribute to cancer both as an oncogene supporting metastasis and as tumour suppressor in different types of tissue. A better understanding of the cancer mechanistics involving tensins may provide the rationale for development of specific therapeutic strategies.
Tensins are structural adaptor proteins localized at focal adhesions. Tensins can act as mechanosensors and participate in the transduction of biochemical signals from the extracellular matrix to the cytoskeleton, acting as an interface able to alter cell behavior in responses to changes in their surrounding environment. This review aims to provide a concise summary of the main functions of the four known tensins in cell and cancer biology, their homology and recently unveiled signaling mechanisms. We focus specifically on how tensin 4 (TNS4/Cten) may contribute to cancer both as an oncogene supporting metastasis and as tumour suppressor in different types of tissue. A better understanding of the cancer mechanistics involving tensins may provide the rationale for development of specific therapeutic strategies.Rereading of the genetic origins of cancer: the puzzle of all erashttps://peerj.com/preprints/279522019-09-102019-09-10Berjas AbumsimirYassine KasmiMoulay Mustapha Ennaji
This is a scientific introduction to review the concept of cancer from a purely genetic perspective in which we try to link the development of tumors by the driving force of the evolution of living beings: the mutations. And to prove the assumption that cancer diversity has a parallel route instead of the whole development process of the cell. Calling for expanding the rolling concept of cancer and tumors definition in general. Which may contribute to altering the angle of our vision to this dangerous biological phenomenon. This call is based on the hypothesis that cancer is a genetic phenomenon that has arisen on the margins of the evolution process, that has continued since the beginning of creation. The pieces of evidence and indications that support this view were presented successively.
This is a scientific introduction to review the concept of cancer from a purely genetic perspective in which we try to link the development of tumors by the driving force of the evolution of living beings: the mutations. And to prove the assumption that cancer diversity has a parallel route instead of the whole development process of the cell. Calling for expanding the rolling concept of cancer and tumors definition in general. Which may contribute to altering the angle of our vision to this dangerous biological phenomenon. This call is based on the hypothesis that cancer is a genetic phenomenon that has arisen on the margins of the evolution process, that has continued since the beginning of creation. The pieces of evidence and indications that support this view were presented successively.Effect of modified RNA-binding proteins HuR on biological behavior of bladder cancer T24 cell linehttps://peerj.com/preprints/279312019-08-312019-08-31Kewen ZhengYan SuXiaomin HanQiang Ma
Background: In tumors, the role of human antigen R (HuR) involves regulating tumor cell proliferation, differentiation, apoptosis, angiogenesis, and lymphangiogenesis. Previous studies have revealed the expression of HuR can be detected in bladder cancer and related to biological behavior of malignancy. Methods: T24 cells were transfected by HuR overexpression vector and HuR knockdown vector. The cells were divided into control group, overExp-HuR group and cas9-HuR group. The cell viability after 48 h was detected by MTT, the apoptosis was detected by Annexin V-APC/7-AAD double staining, the cell migration was detected by Transwell assay, and the expression of HuR, cyclinD1 and apoptosis-related factors (Bcl-2) were detected by fluorescence quantitative PCR and Western blot. Results: Compared with the control group, the cell viability after 48 h in the overExp-HuR group increased significantly, and decreased in the cas9-HuR group (P<0.05). And the number of migrating cells increased in the overExp-HuR group, and decreased in the cas9-HuR group (P<0.05). The apoptosis rate of the overExp-HuR group decreased significantly, and increased significantly in the cas9-HuR group (P<0.05). The mRNA and protein expression of HuR, cyclinD1 and Bcl-2 of the overExp-HuR group increased, and decreased significantly in cas9-HuR group (P<0.05). Conclusion: HuR promote the proliferation and migration of T24 cells, and inhibit cell apoptosis. And the mechanism may be related to the expression of cyclin D and apoptosis-related proteins Bcl2.
Background: In tumors, the role of human antigen R (HuR) involves regulating tumor cell proliferation, differentiation, apoptosis, angiogenesis, and lymphangiogenesis. Previous studies have revealed the expression of HuR can be detected in bladder cancer and related to biological behavior of malignancy. Methods: T24 cells were transfected by HuR overexpression vector and HuR knockdown vector. The cells were divided into control group, overExp-HuR group and cas9-HuR group. The cell viability after 48 h was detected by MTT, the apoptosis was detected by Annexin V-APC/7-AAD double staining, the cell migration was detected by Transwell assay, and the expression of HuR, cyclinD1 and apoptosis-related factors (Bcl-2) were detected by fluorescence quantitative PCR and Western blot. Results: Compared with the control group, the cell viability after 48 h in the overExp-HuR group increased significantly, and decreased in the cas9-HuR group (P<0.05). And the number of migrating cells increased in the overExp-HuR group, and decreased in the cas9-HuR group (P<0.05). The apoptosis rate of the overExp-HuR group decreased significantly, and increased significantly in the cas9-HuR group (P<0.05). The mRNA and protein expression of HuR, cyclinD1 and Bcl-2 of the overExp-HuR group increased, and decreased significantly in cas9-HuR group (P<0.05). Conclusion: HuR promote the proliferation and migration of T24 cells, and inhibit cell apoptosis. And the mechanism may be related to the expression of cyclin D and apoptosis-related proteins Bcl2.Allogenic stem cell transplant in a patient with classical Kaposi's sarcomahttps://peerj.com/preprints/482019-08-042019-08-04Richard Barchas
A 68 year old male with a history of classical Kaposi's sarcoma (KS) and precursor T-cell acute lymphoblastic leukemia (ALL) received an allogenic stem cell transplant from an unrelated donor to treat his ALL. He developed acute graft-vs.-host-disease (GVHD) which was treated by increasing immunosuppressants. KS, which had been in remission for years, then recurred aggressively. Tapering immunosuppressants to treat the KS was not possible because of GVHD. Chemotherapy could not be used because of its adverse effect on the bone marrow so soon after transplant. The only option was to use antiviral therapy (cidofovir) to lower the level of HHV-8, the virus that is a causal factor in KS. Although HHV-8 levels were significantly reduced, new KS lesions continued to appear. The patient developed acute kidney injury after the third cidofovir infusion and died from renal and respiratory failure soon afterward. Post-mortem revealed extensive internal KS lesions involving multiple organs. Based on the experience with this patient, allogenic transplant using an unrelated donor has been found to be a questionable treatment modality for classical KS patients requiring treatment for another condition such as leukemias and lymphomas. Post-transplant immunosuppression is required to prevent GVHD, and if it occurs, immunosuppression may have to be increased. Aggressive KS developed in this patient under these conditions, and could not be controlled by tapering immunosuppressants. Although the risk of GVHD is lower for an allogenic transplant using a matched sibling instead of an unrelated donor, the risk of both GVHD and aggressive KS both developing may still be unacceptably high.Alternative treatment modalities for these patients might include continuing with chemotherapy and autologous transplant. These avoid GVHD and lower the need for long term immunosuppression, but have a much higher risk of relapse of the underlying malignancy. Still, they could be preferable to an allogenic transplant for such cases.
A 68 year old male with a history of classical Kaposi's sarcoma (KS) and precursor T-cell acute lymphoblastic leukemia (ALL) received an allogenic stem cell transplant from an unrelated donor to treat his ALL. He developed acute graft-vs.-host-disease (GVHD) which was treated by increasing immunosuppressants. KS, which had been in remission for years, then recurred aggressively. Tapering immunosuppressants to treat the KS was not possible because of GVHD. Chemotherapy could not be used because of its adverse effect on the bone marrow so soon after transplant. The only option was to use antiviral therapy (cidofovir) to lower the level of HHV-8, the virus that is a causal factor in KS. Although HHV-8 levels were significantly reduced, new KS lesions continued to appear. The patient developed acute kidney injury after the third cidofovir infusion and died from renal and respiratory failure soon afterward. Post-mortem revealed extensive internal KS lesions involving multiple organs. Based on the experience with this patient, allogenic transplant using an unrelated donor has been found to be a questionable treatment modality for classical KS patients requiring treatment for another condition such as leukemias and lymphomas. Post-transplant immunosuppression is required to prevent GVHD, and if it occurs, immunosuppression may have to be increased. Aggressive KS developed in this patient under these conditions, and could not be controlled by tapering immunosuppressants. Although the risk of GVHD is lower for an allogenic transplant using a matched sibling instead of an unrelated donor, the risk of both GVHD and aggressive KS both developing may still be unacceptably high.Alternative treatment modalities for these patients might include continuing with chemotherapy and autologous transplant. These avoid GVHD and lower the need for long term immunosuppression, but have a much higher risk of relapse of the underlying malignancy. Still, they could be preferable to an allogenic transplant for such cases.Melatonin combination with perindopril alleviated doxorubicin cardiac toxicity in L-NAME hypertensive rats: comparative study with perindoprilhttps://peerj.com/preprints/278632019-07-182019-07-18Takwa Mohammed Abdul SalamAmany Helmy HasaninWesam El-BaklyMona Hussein RaafatNesreen OmarAhmed El Sayed Badawy
Introduction: Doxorubicin is a highly effective anticancer agent with serious cardiotoxic effects. Hypertension is considered as a major risk factor for doxorubicin cardiotoxicity. It should be noted that about one-third of cancer patients have hypertension, and melatonin can have cardio-protective effects. The present study aimed to further investigate the possible beneficial effects of melatonin co-administration to perindopril against doxorubicin cardiotoxicity in hypertensive rats. Method: Rats were randomly assigned to naïve group and L-NAME group, which was further subdivided into untreated, doxorubicin, doxorubicin/perindopril, doxorubicin/melatonin and doxorubicin/perindopril/melatonin subgroups. Cardiac functions, CK-MB, malondialdehyde, superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and cardiac percentage area of collagen fibers were evaluated. Results: Combining melatonin with perindopril to doxorubicin produced significant decreases in left ventricular end diastolic pressure, malondialdehyde, TNF-α, and TGF-β. It resulted in significant increases in left ventricular dP/dtmax and SOD, in addition to apparent improvement in cardiac histopathology with a significant decrease in percentage area of collagen deposition compared to perindopril alone. Conclusion: Co-administration of melatonin to perindopril in hypertensive rats who received doxorubicin alleviated doxorubicin cardiac toxicity more than using perindopril alone. These effects could be explained by the reported antihypertensive, anti-inflammatory, anti-oxidant, and anti-fibrotic effects of melatonin.
Introduction: Doxorubicin is a highly effective anticancer agent with serious cardiotoxic effects. Hypertension is considered as a major risk factor for doxorubicin cardiotoxicity. It should be noted that about one-third of cancer patients have hypertension, and melatonin can have cardio-protective effects. The present study aimed to further investigate the possible beneficial effects of melatonin co-administration to perindopril against doxorubicin cardiotoxicity in hypertensive rats. Method: Rats were randomly assigned to naïve group and L-NAME group, which was further subdivided into untreated, doxorubicin, doxorubicin/perindopril, doxorubicin/melatonin and doxorubicin/perindopril/melatonin subgroups. Cardiac functions, CK-MB, malondialdehyde, superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and cardiac percentage area of collagen fibers were evaluated. Results: Combining melatonin with perindopril to doxorubicin produced significant decreases in left ventricular end diastolic pressure, malondialdehyde, TNF-α, and TGF-β. It resulted in significant increases in left ventricular dP/dtmax and SOD, in addition to apparent improvement in cardiac histopathology with a significant decrease in percentage area of collagen deposition compared to perindopril alone. Conclusion: Co-administration of melatonin to perindopril in hypertensive rats who received doxorubicin alleviated doxorubicin cardiac toxicity more than using perindopril alone. These effects could be explained by the reported antihypertensive, anti-inflammatory, anti-oxidant, and anti-fibrotic effects of melatonin.Synthesis, characterization, and biological evaluation of new spebrutinib analogues: potential candidates with enhanced activity and reduced toxicity profileshttps://peerj.com/preprints/277552019-05-242019-05-24Zaid M Jaber Al-ObaidiOmar F Abdul-RasheedMonther F MahdiAyad M R Raauf
Background: Cancer is regarded as an undoubtable major concern for both researchers and the general public because of its high mortality rates. While breast cancer has the highest incidence of malignancy globally, colon cancer also has high morbidity and mortality rates. Currently, researchers are working on designing, synthesizing, and biologically investigating the effects of some potential anticancer candidates.
Methods: The authors successfully synthesized and characterized two potential spebrutinib analogues. These analogues were evaluated with the employment of MCF-7, HCT116, and MDCK cell lines.
Results: With respect to the spebrutinib standard, one of these analogues had superior activity against the MCF-7 cell line (IC50; 10.744 µg/mL against 13.566 µg/mL for spebrutinib) and an enhanced toxicity profile on the MDCK cell line (IC50; 8.653 mg/mL against 4.011 mg/mL for spebrutinib).
Background: Cancer is regarded as an undoubtable major concern for both researchers and the general public because of its high mortality rates. While breast cancer has the highest incidence of malignancy globally, colon cancer also has high morbidity and mortality rates. Currently, researchers are working on designing, synthesizing, and biologically investigating the effects of some potential anticancer candidates.Methods: The authors successfully synthesized and characterized two potential spebrutinib analogues. These analogues were evaluated with the employment of MCF-7, HCT116, and MDCK cell lines.Results: With respect to the spebrutinib standard, one of these analogues had superior activity against the MCF-7 cell line (IC50; 10.744 µg/mL against 13.566 µg/mL for spebrutinib) and an enhanced toxicity profile on the MDCK cell line (IC50; 8.653 mg/mL against 4.011 mg/mL for spebrutinib).Standardized representation of the LIDC annotations using DICOMhttps://peerj.com/preprints/273782019-05-202019-05-20Andrey FedorovMatthew HancockDavid ClunieMathias BrochhausenJonathan BonaJustin KirbyJohn FreymannSteve PieperHugo AertsRon KikinisFred Prior
The Lung Imaging Data Consortium and Image Database Resource Initiative (LIDC) conducted a multi-site reader study that produced a comprehensive database of Computed Tomography (CT) scans for over 1000 subjects annotated by multiple expert readers. The result is hosted in the LIDC-IDRI collection of The Cancer Imaging Archive (TCIA). Annotations that accompany the images of the collection are stored using project-specific XML representation. This complicates their reuse, since no general-purpose tools are available to visualize or query those objects, and makes harmonization with other similar type of data non-trivial. To make the LIDC dataset more FAIR (Findable, Accessible, Interoperable, Reusable) to the research community, we prepared their standardized representation using the Digital Imaging and Communications in Medicine (DICOM) standard. This manuscript is intended to serve as a companion to the dataset to facilitate its reuse.
The Lung Imaging Data Consortium and Image Database Resource Initiative (LIDC) conducted a multi-site reader study that produced a comprehensive database of Computed Tomography (CT) scans for over 1000 subjects annotated by multiple expert readers. The result is hosted in the LIDC-IDRI collection of The Cancer Imaging Archive (TCIA). Annotations that accompany the images of the collection are stored using project-specific XML representation. This complicates their reuse, since no general-purpose tools are available to visualize or query those objects, and makes harmonization with other similar type of data non-trivial. To make the LIDC dataset more FAIR (Findable, Accessible, Interoperable, Reusable) to the research community, we prepared their standardized representation using the Digital Imaging and Communications in Medicine (DICOM) standard. This manuscript is intended to serve as a companion to the dataset to facilitate its reuse.Sex Matters in Health and Disease: a review of biological sex differences with an emphasis on gliomahttps://peerj.com/preprints/277162019-05-092019-05-09Susan Christine MasseyPaula WhitmireTatum E DoyleJoseph E IppolitoMaciej M MrugalaLeland S HuPeter CanollAlexander R A AndersonMelissa A WilsonSusan M FitzpatrickMargaret M McCarthyJoshua B RubinKristin R Swanson
Humans are sexually dimorphic, with sex being the most persistent difference among humans over the course of our evolutionary history. Beyond the visible sex differences that can be considered true dimorphisms, there are also sex differences at the molecular and cellular scales. The role of these biological sex differences for human health, while being increasingly recognized, have long been underappreciated and underexplored. Frequently, these differences are only recognized in sex–specific diseases, such as genitourinary diseases and cancers. However, given the evidence for sex differences in the most basic aspects of human biology, including metabolism, cellular composition, and immune activity, these differences could have consequences for the etiology and pathophysiology of a majority of diseases. It is thus essential to consider the extent to which these differences may influence the various mechanisms underlying disease processes, response to treatment, and the maintenance of health in order to better improve patient outcomes. Here we review the evidence for a broad array of biological sex differences in humans and discuss how they may relate to observed sex differences in various diseases, with an emphasis on cancer, specifically glioblastoma. We further propose that mathematical approaches can be useful for exploring the extent to which sex differences affect disease outcomes and accounting for those in the development of therapeutic strategies.
Humans are sexually dimorphic, with sex being the most persistent difference among humans over the course of our evolutionary history. Beyond the visible sex differences that can be considered true dimorphisms, there are also sex differences at the molecular and cellular scales. The role of these biological sex differences for human health, while being increasingly recognized, have long been underappreciated and underexplored. Frequently, these differences are only recognized in sex–specific diseases, such as genitourinary diseases and cancers. However, given the evidence for sex differences in the most basic aspects of human biology, including metabolism, cellular composition, and immune activity, these differences could have consequences for the etiology and pathophysiology of a majority of diseases. It is thus essential to consider the extent to which these differences may influence the various mechanisms underlying disease processes, response to treatment, and the maintenance of health in order to better improve patient outcomes. Here we review the evidence for a broad array of biological sex differences in humans and discuss how they may relate to observed sex differences in various diseases, with an emphasis on cancer, specifically glioblastoma. We further propose that mathematical approaches can be useful for exploring the extent to which sex differences affect disease outcomes and accounting for those in the development of therapeutic strategies.Schedule feasibility and workflow for additive manufacturing of titanium plates for cranioplasty reconstruction in canine skull tumorshttps://peerj.com/preprints/277072019-05-062019-05-06Jordan JamesMichelle L OblakAlex zur LindenFiona MK JamesMatt ParkesJohn Phillips
Additive manufacturing has allowed for the creation of a patient-specific custom solution that can resolve many of the limitations previously reported for canine cranioplasty. The purpose of this pilot study was to determine the schedule feasibility and workflow in manufacturing patient-specific titanium implants for canines undergoing cranioplasty immediately following craniectomy. Computed tomography scans from patients with tumors of the skull were considered and 3 cases were selected. Images were imported into OsiriX MD image processing software and tumor margins were determined based on agreement between a board-certified veterinary radiologist and veterinary surgical oncologist. Virtual surgical planning was performed and a 5mm bone margin was selected. A defect was created to simulate the intraoperative defect. Stereolithography format files of the skulls were imported into Renishaw Additive-manufacture for Design-led Efficient Patient Treatment (ADEPT) software. In collaboration with medical solution center, Additive Design in Surgical Solutions (ADEISS), a custom titanium plate was designed with the input of an applications engineer and veterinary surgical oncologist. Plates were printed in titanium and postprocessed at ADEISS. Total planning time was approximately 2 hours with a manufacturing time of 2 weeks. Based on the findings of this study, with access to an advanced 3D metal printing medical solution center that can provide advanced software and printing, patient-specific additive manufactured titanium implants can be planned, created, processed, shipped and sterilized for patient use within a 3-week turnaround.
Additive manufacturing has allowed for the creation of a patient-specific custom solution that can resolve many of the limitations previously reported for canine cranioplasty. The purpose of this pilot study was to determine the schedule feasibility and workflow in manufacturing patient-specific titanium implants for canines undergoing cranioplasty immediately following craniectomy. Computed tomography scans from patients with tumors of the skull were considered and 3 cases were selected. Images were imported into OsiriX MD image processing software and tumor margins were determined based on agreement between a board-certified veterinary radiologist and veterinary surgical oncologist. Virtual surgical planning was performed and a 5mm bone margin was selected. A defect was created to simulate the intraoperative defect. Stereolithography format files of the skulls were imported into Renishaw Additive-manufacture for Design-led Efficient Patient Treatment (ADEPT) software. In collaboration with medical solution center, Additive Design in Surgical Solutions (ADEISS), a custom titanium plate was designed with the input of an applications engineer and veterinary surgical oncologist. Plates were printed in titanium and postprocessed at ADEISS. Total planning time was approximately 2 hours with a manufacturing time of 2 weeks. Based on the findings of this study, with access to an advanced 3D metal printing medical solution center that can provide advanced software and printing, patient-specific additive manufactured titanium implants can be planned, created, processed, shipped and sterilized for patient use within a 3-week turnaround.Identification of key gene modules and genes in colorectal cancer by weighted gene co-expression network analysis (WGCNA)https://peerj.com/preprints/276672019-04-192019-04-19Zheying ZhangNa LiQingzu GaoXinlai Qian
Background: Colorectal cancer (CRC) is a malignant tumor particularly common in developing countries. In this study, we used Weighted Gene Co-Expression Network Analysis (WGCNA) of chip data and screened hub genes in CRC to find the gene modules specifically correlated with clinical traits. Methods: WGCNA was used to identify the gene modules specifically associated with metastasis in colorectal cancer. Cytoscape software was used to construct a co-expression network. The expression of CYTH1 was determined by qRT-PCR. Results: Based on the predicted co-expression network, we identified that the turquoise module was associated with CRC clinical metastasis traits. Turquoise module genes were analyzed, and we identified the hub gene CYTH1 using Cytoscape software. Additionally, we found CYTH1’s expression was lower in CRC tissue and cells when compared with normal counterparts.
Background: Colorectal cancer (CRC) is a malignant tumor particularly common in developing countries. In this study, we used Weighted Gene Co-Expression Network Analysis (WGCNA) of chip data and screened hub genes in CRC to find the gene modules specifically correlated with clinical traits. Methods: WGCNA was used to identify the gene modules specifically associated with metastasis in colorectal cancer. Cytoscape software was used to construct a co-expression network. The expression of CYTH1 was determined by qRT-PCR. Results: Based on the predicted co-expression network, we identified that the turquoise module was associated with CRC clinical metastasis traits. Turquoise module genes were analyzed, and we identified the hub gene CYTH1 using Cytoscape software. Additionally, we found CYTH1’s expression was lower in CRC tissue and cells when compared with normal counterparts.