scholarly journals Patient-individual cancer cell lines and tissue analysis delivers no evidence of sequences from DNA viruses in colorectal cancer cells

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Michael Gock ◽  
Marcel Kordt ◽  
Stephanie Matschos ◽  
Christina S. Mullins ◽  
Michael Linnebacher

Abstract Background Several DNA viruses are highly suspicious to have oncogenic effects in humans. This study investigates the presence of potentially oncogenic viruses such as SV40, JCV, BKV and EBV in patient-derived colorectal carcinoma (CRC) cells typifying all molecular subtypes of CRC. Methods Sample material (gDNA and cDNA) of a total of 49 patient-individual CRC cell lines and corresponding primary material from 11 patients, including normal, tumor-derived and metastasis-derived tissue were analyzed for sequences of SV40, JVC, BKV and EBV using endpoint PCR. In addition, the susceptibility of CRC cells to JCV and BKV was examined using a long-term cultivation approach of patient-individual cells in the presence of viruses. Results No virus-specific sequences could be detected in all specimens. Likewise, no morphological changes were observed and no evidence for viral infection or integration could be provided after long term CRC cell cultivation in presence of viral particles. Conclusions In summary, the presented data suggest that there is no direct correlation between tumorigenesis and viral load and consequently no evidence for a functional role of the DNA viruses included into this analysis in CRC development.

2020 ◽  
Author(s):  
Michael Gock ◽  
Marcel Kordt ◽  
Stephanie Matschos ◽  
Christina S. Mullins ◽  
Michael Linnebacher

Abstract Background: Several DNA viruses are highly suspicious to have oncogenic effects in humans. This study investigates the presence of potentially oncogenic viruses such as SV40, JCV, BKV and EBV in patient-derived colorectal carcinoma (CRC) cells typifying all molecular subtypes of CRC. Methods: Sample material (gDNA and cDNA) of a total of 49 patient-individual CRC cell lines and corresponding primary material from 11 patients, including normal, tumor-derived and metastasis-derived tissue were analyzed for sequences of SV40, JVC, BKV and EBV using endpoint PCR. In addition, the susceptibility of CRC cells to JCV and BKV was examined using a long-term cultivation approach of patient-individual cells in the presence of viruses. Results: No virus-specific sequences could be detected in all specimens. Likewise, no morphological changes were observed and no evidence for viral infection or integration could be provided after long term CRC cell cultivation in presence of viral particles. Conclusions: In summary, the presented data suggest that there is no direct correlation between tumorigenesis and viral load and consequently no evidence for a functional role of the DNA viruses included into this analysis in CRC development.


2020 ◽  
Author(s):  
Michael Gock(Former Corresponding Author) ◽  
Marcel Kordt ◽  
Stephanie Matschos ◽  
Christina S. Mullins ◽  
Michael Linnebacher(New Corresponding Author)

Abstract Background Several DNA viruses are highly suspicious to have oncogenic effects in humans. This study investigates the presence of potentially oncogenic viruses such as SV40, JCV, BKV and EBV in patient-derived colorectal carcinoma (CRC) cells typifying all molecular subtypes of CRC. Methods Sample material (gDNA and cDNA) of a total of 49 patient-individual CRC cell lines and corresponding primary material from 11 patients, including normal, tumor-derived and metastasis-derived tissue were analyzed for sequences of SV40, JVC, BKV and EBV using endpoint PCR. In addition, the susceptibility of CRC cells to JCV and BKV was examined using a long-term cultivation approach of patient-individual cells in the presence of viruses. Results No virus-specific sequences could be detected in all specimens. Likewise, no morphological changes were observed and no evidence for viral infection or integration could be provided after long term CRC cell cultivation in presence of viral particles. Conclusions In summary, the presented data suggest that there is no direct correlation between tumorigenesis and viral load and consequently no evidence for a functional role of the DNA viruses included into this analysis in CRC development.


2019 ◽  
Author(s):  
Michael Gock ◽  
Marcel Kordt ◽  
Stephanie Matschos ◽  
Christina S. Mullins ◽  
Michael Linnebacher

Abstract Background Several DNA viruses are highly suspicious to have oncogenic effects in humans. This study investigates the presence of potentially oncogenic viruses such as SV40, JCV, BKV and EBV in patient-derived colorectal carcinoma (CRC) cells typifying all molecular subtypes of CRC. Methods Sample material (gDNA and cDNA) of a total of 49 patient-individual CRC cell lines and corresponding primary material from 11 patients, including normal, tumor-derived and metastasis-derived tissue were analyzed for sequences of SV40, JVC, BKV and EBV using endpoint PCR. In addition, the susceptibility of CRC cells to JCV and BKV was examined using a long-term cultivation approach of patient-individual cells in the presence of viruses. Results No virus-specific sequences could be detected in all specimens. Likewise, no morphological changes were observed and no evidence for viral infection or integration could be provided after long term CRC cell cultivation in presence of viral particles. Conclusions In summary, the presented data suggest that there is no direct correlation between tumorigenesis and viral load and consequently no evidence for a functional role of the DNA viruses included into this analysis in CRC development.


2020 ◽  
Author(s):  
Michael Gock ◽  
Marcel Kordt ◽  
Stephanie Matschos ◽  
Christina S. Mullins ◽  
Michael Linnebacher

Abstract Background Several DNA viruses are highly suspicious to have oncogenic effects in humans. This study investigates the presence of potentially oncogenic viruses such as SV40, JCV, BKV and EBV in patient-derived colorectal carcinoma (CRC) cells typifying all molecular subtypes of CRC.Methods Sample material (gDNA and cDNA) of a total of 49 patient-individual CRC cell lines and corresponding primary material from 11 patients, including normal, tumor-derived and metastasis-derived tissue were analyzed for sequences of SV40, JVC, BKV and EBV using endpoint PCR. In addition, the susceptibility of CRC cells to JCV and BKV was examined using a long-term cultivation approach of patient-individual cells in the presence of viruses.Results No virus-specific sequences could be detected in all specimens. Likewise, no morphological changes were observed and no evidence for viral infection or integration could be provided after long term CRC cell cultivation in presence of viral particles.Conclusions In summary, the presented data suggest that there is no direct correlation between tumorigenesis and viral load and consequently no evidence for a functional role of the DNA viruses included into this analysis in CRC development.


2021 ◽  
Vol 43 (2) ◽  
pp. 77-78
Author(s):  
M. S. Todortseva

Taking into account the great interest in identifying the role of the nervous system in the processes of tumor growth and the insufficient study of morphological changes in the nervous apparatus of neoplasms, in our clinic (Head - Prof. AM Foy), since 1955, work has been carried out to study the effect of prolonged hyperestrogenism on the nervous apparatus of the uterus during the development of experimental fibroids in it. Experiments with long-term administration of estrogenic hormones were carried out on 120 non-castrated female guinea pigs weighing from 150.0 to 250.0, which were divided into 4 groups.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 414-414
Author(s):  
C. Grandclement ◽  
R. Bedel ◽  
B. Kantelip ◽  
E. Viel ◽  
J. Remy Martin ◽  
...  

414 Background: Initially characterized as neuronal receptors, Neuropilins (NRPs) were also found to be expressed in endothelial cells and subsequently were shown to play a role in the development of the vascular system. NRP family consists of two genes, neuropilin-1 (NRP1) and neuropilin-2 (NRP2).The multiple functions of NRPs were recently highlighted by the identification of NRP role in oncogenesis. In this study, we first confirmed the role of NRP2 in tumor progression. We also extended the understanding of NRP2 oncogenic functions by investigating the ability of NRP2 to orchestrate epithelial-mesenchymal transition (EMT) in colorectal cancer cells. Methods: We have generated human colon cancer cell lines transfected with NRP2 transgene or siRNA to investigate NRP2 involvement in EMT. First, the oncogenic functions of NRP2 were studied in vitro by MTT, soft agar, invasion assays and in vivo using xenografts experiments. Ability of NRP2 to orchestrate EMT was then investigated by flow cytometry, immunohistochemical (IHC) staining, western-blotting and quantitative real-time PCR. Results: IHC staining revealed that NRP2 is expressed in human colon and breast carcinomas while it is not expressed in healthy tissues. Then, we confirmed that NRP2 increases tumor proliferation, colony formation, invasion and xenograft formation. Moreover, NRP2-expressing cells displayed an immunohistochemical phenotype of EMT characterized by the loss of E-Cadherin and an increase of vimentin. Furthermore, NRP2 expression promotes transforming-growth factor-β1 (TGF- β1) signaling, leading to an increased phosphorylation of the Smad2/3 complex in colorectal cancer cell lines. Specific inhibition of NRP2 using siRNA or treatment with specific TGFβRI kinase inhibitors prevented this phosphorylation and the EMT, suggesting that NRP2 cooperates with TGFRI to promote EMT in colorectal carcinoma. Conclusions: Our findings have reinforced the essential role of NRP2 in cancer progression and demonstrated that NRP2 expression confers to tumor cell lines the hallmarks of EMT. Moreover, in the current work, we present evidence for the therapeutic value of NRP2 targeting. No significant financial relationships to disclose.


2010 ◽  
Vol 58 (2) ◽  
pp. 243-256 ◽  
Author(s):  
Ján Varga ◽  
Pavel Staško ◽  
Štefan Tóth ◽  
Zuzana Pristášová ◽  
Zuzana Jonecová ◽  
...  

Ischaemic/reperfusion (IR) injury of the small intestine may lead to the development of multiple organ failure. Little is known about the morphological changes occurring in the organs during the subacute course of this syndrome. The objective of this study was to observe histopathological features and the role of apoptosis in the jejunal mucosa and lung parenchyma after intestinal IR injury in a long-term experiment. Wistar rats (n = 36) were divided into 4 experimental groups (IR 10 , IR 20 , IR 30 , S). Groups IR 10 , IR 20 and IR 30 (each n = 10) were subjected to 1-hour ischaemia of the cranial mesenteric artery followed by 10, 20 or 30 days of reperfusion, respectively. The control group S (n = 6) was not subjected to ischaemia. The jejunal mucosa remained intact after all periods of reperfusion. Apoptotic cells were found particularly in the lamina propria, with the most significant difference observed in the IR 30 group (P < 0.01). The lung parenchyma had lower regenerative capacity, which was confirmed by a high index of histological damage after 30 days of reperfusion (P < 0.01) and by the presence of an increased number of apoptotic cells, especially in the pulmonary interstitium. The number of apoptotic cells was ten times higher than in the control group (P < 0.001).


2013 ◽  
Vol 6 (2) ◽  
pp. 121-125 ◽  
Author(s):  
Francesco Arcuri ◽  
Matteo Brucoli ◽  
Nicola Baragiotta ◽  
Livia Stellin ◽  
Mariangela Giarda ◽  
...  

PurposeThe first autologous adipose tissue grafting was performed by Neuber in 1893 with an open approach. In the early 1980s, Illouz and Fournier introduced closed liposuction. In the 1990s, Coleman published a new method of atraumatic fat transplantation. Recently, immunohistochemical studies of the extracellular matrix of the lipoaspirate showed the presence of adipose-derived stem cells. The purpose of this study is to describe the role of fat grafting in the management of posttraumatic facial deformities.MethodsThe study population was composed of all patients who underwent facial fat grafting between March 2008 and November 2010 as a secondary reconstructive procedure after an initial unsatisfactory treatment of the skeletal fractures. We analyzed the postoperative morphological changes by comparing the grafted side of the face to the contralateral side with the aid of a software package.ResultsNineteen patients were surgically treated with fat transplantation for facial asymmetry due to a pathological postoperative healing of the soft tissue. Clinical examination and software analysis showed adequate postoperative facial balance without major complications.ConclusionFat grafting is a very powerful tool to correct posttraumatic maxillofacial deformities and to ensure a long-term follow-up. Although we have achieved excellent clinical results in our reconstructive clinical cases, we are convinced that more complex prospective studies, enriched by long-term radiological controls, are needed to fully understand the biological behavior of the transplanted fat in the posttraumatic face.


Author(s):  
Jennifer A. Millington ◽  
Colin A. Booth ◽  
Michael A. Fullen ◽  
Glenis M. Moore ◽  
Ian C. Trueman ◽  
...  

Attitudes to maintaining dune diversity are changing under the realization that existing dune stabilization techniques are fixing dune landscapes, causing ‘coastal squeeze’ and loss of habitat as shorelines retreat. Instead, it is recommended that a natural, dynamic, migrating dune system is much more appropriate and that blown, unstable sands are encouraged to act as mobile coastal defence barriers. Lack of appropriate monitoring techniques has limited progress in understanding the role of sediment dynamics in dune environments over long timescales. Therefore, this paper outlines the role of straightforward and inexpensive photography, from fixed points and angles, as a useful approach to long‐term, decadal monitoring of the evolution and migration of dynamic dune landforms. The case study, on the Morfa Dyffryn dunes, Gwynedd, mid‐Wales, United Kingdom (National Grid Reference SH563240), identified particularly dynamic mobile fo‐redunes, with cyclical morphological development, paralleling to an overall landward recession. A cyclical trend of sand encroachment, followed by stabilization with growing vegetation, is documented for semi‐fixed dune pastures, while the hind dunes remained stable. A general relationship between foredune morphology and erosion/accretion processes was established, offering the prospect of predicting future dune morphological changes in other dune systems, if increased blown sand activity is encouraged as a management technique. Santrauka Požiūris išlaikyti kopų įvairovę kinta, suvokiant, kad esamos kopų stabilizavimo priemonės, formuojant kopų kraštovaizdį, nepadeda išvengti pajūrio ruožo susiaurėjimo ir arealo praradimo atsitraukiant kranto linijai. Kita vertus, rekomenduojama išsaugoti natūralią dinamišką ir migruojančią kopų sistemą, kad nupustomi labilūs smėliai atliktų mobilių kranto apsaugos barjerų funkciją. Dėl tinkamų monitoringo priemonių trūkumo sulėtėjo patirties apie ilgalaikę nuosėdų dinamiką kopų aplinkoje kaupimas. Darbe aprašomas tiesioginis ir didelių išlaidų nereikalaujantis fotografijos metodas, kuris galėtų būti taikomas minėtoms problemoms spręsti. Metodas pagrįstas fotografavimu fiksuotuose taškuose ir tomis pačiomis kryptimis. Tai gali būti naudingas būdas ilgalaikiam monitoringui – stebėti dinaminių kopų sausumos darinių migraciją dešimtmečius. Tiriamoji vieta – Morfa Dyffryn kopos, Gwynedd, Velso vidurinėje dalyje Jungtinėje Karalystėje (nacionalinėje koordinačių sistemoje SH563240). Tai ypač dinamiškos priešakinės kopos. Joms būdinga cikliška morfologinė raida, prilygstanti bendrajam atsitraukimui iš sausumo pusės. Cikliška smėlio įsibrovimo tendencija, po kurio vyksta augalijos stabilizavimasis, būdinga pusiau sutvirtintoms kopoms, kai užnugarinės kopos lieka stabilios. Darbe nustatytos bendros sąsajos tarp priešakinių kopų morfologijos ir erozijos/akrecijos procesų, siūlomas morfologinių pokyčių numatymo būdas, kuris galėtų tapti valdymo priemone ir kitose kopų sistemose, kur smėlis ypač pustomas. Резюме Мнение о том, как сохранить разнообразие дюн, меняется, если принять во внимание, что существующие способы стабилизации дюн формируют ландшафт с дюнами, „сжимают“ приморье и теряют ареал из-за отступления линии берега. С другой стороны, рекомендуется сохранить естественную, динамичную и мигрирующую систему, чтобы сдуваемые, подвижные пески служили мобильными барьерами для защиты берега. Из-за нехватки соответствующих средств мониторинга замедлилось получение сведений о многолетней динамике отложений в среде дюн. С целью восполнить пробел в статье описывается не требующий больших затрат метод фотографирования. Он основан на фотографировании в фиксированных точках и в тех же направлениях и может стать полезным способом осуществления многолетнего мониторинга миграции динамичных дюн. Исследования проводились в динамичных передних дюнах Morfa Dyffryn, Gwynedd, в средней части Уэльса в Англии (в Национальной системе координат SH563240). Для них характерно цикличное морфологическое развитие, соответствующее общему отступлению со стороны суши. Цикличная тенденция наступления песка, после чего стабилизируется растительность, характерна для отчасти укрепленных дюн в том случае, если задние дюны остаются стабильными. Установлена связь между процессами морфологии передних дюн и эрозии/аккреции, предложен способ предвидения морфологических изменений в качестве средства управления процессом и в других системах дюн, в которых усилилась деятельность подвижного песка.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi196-vi197
Author(s):  
Anshu Malhotra ◽  
Jingbo Liu ◽  
Tobey MacDonald

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children. Of the four different sub-groups, the Sonic Hedgehog (SHH) subgroup accounts for about 30% of human MBs. The current standard of care (resection, cranio-spinal irradiation, and chemotherapy) for MB is typically ineffective for SHH MB in non-infants and those with metastatic disease. Survivors are frequently beset with long-term side effects including cognitive deficiencies and a severely impaired quality of life. Taken together, there is a critical need for novel targeted therapies for SHH MB. Recently, promising preclinical and clinical results have been obtained in a variety of cancers treated with a small molecule antagonist, ONC-201, which acts against DRD2, a G-protein coupled receptor that is widely expressed in MBs and regulates pro-survival pathways in tumors. In the present study we report the activity of ONC-201 and another DRD2 antagonist, ONC-206, which binds DRD2 with increased affinity. We tested three different MB cell lines with varied levels of DRD2 expression against these drugs, and consistently observed increased cell death at lower doses of ONC-206 compared to ONC-201. Following literature reports about the mechanism of action of ONC-201, we also evaluated the role of ClpP gene in MB cell lines. ClpP is a mitochondrial protease that has been shown to directly bind ONC 201. We observed a decrease in the expression of this gene after treatment of MB cell lines with ONC-206. Current studies are focusing on exploring the mechanism by which ONC-206 affects MB growth and metastasis. Dissecting this mechanism will be pivotal in predicting the role of this small molecule as a pre-clinical therapeutic for MB treatment.


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