Scientific Publications
Scientific publications and exciting articles where PreciPoint products and solutions were successfully used.
Alwosaibai, Kholoud; Aalmri, Salmah; Mashhour, Miral; Ghandorah, Salim; Alshangiti, Abdulraheem; Azam, Faisal; Selwi, Waleed; Gharaibeh, Lubna; Alatawi, Yasser; Alruwaii, Zainab; Alsaab, Hashem O.
M8 Microscope and Scanner and ViewPoint Software Unlocks PD-L1 Expression Activities in Ovarian Cancer Dynamics
Researchers investigated the potential of immune checkpoint inhibitors, specifically PD-L1 inhibitors, in treating ovarian cancer with the help of M8 microscope and scanner and ViewPoint software. Surprisingly, they found high PD-L1 expressions in 47.8% of ovarian cancer samples, spanning various epithelial ovarian cancer types. Contrary to expectations, high PD-L1 expression wasn\'t linked to poor prognosis. Additionally, 81% of ovarian cancer samples exhibited TILs expressing both CD8 and CD4, significantly correlating with elevated PD-L1 levels. Furthermore, high PD-L1 expression was associated with stem cell markers CD44 and LGR5, hinting at a connection between immune response, stem cells, and ovarian cancer. PD-L1 overexpression, especially in serous ovarian carcinomas, didn\'t impact overall survival rates. This finding underscores the intricate interplay between PD-L1, TILs, and cancer stem cells, suggesting that inhibiting PD-L1 with immune checkpoint inhibitors might curtail the stem cell population linked to cancer recurrence.
Result: Anti-CD8 (clone 4B11) mouse monoclonal antibody and Anti-CD4 (clone 4B12) mouse monoclonal antibody were used with a dilution ratio of 1:100 for tumor-infiltrating lymphocytes. The subsequent immunoreactivity was observed using M8 digital microscope and scanner. The specimen was further imaged and analyzed using ViewPoint Virtual Slide Viewing Software.
@article{nokeyo,
title = {PD-L1 is highly expressed in ovarian cancer and associated with cancer stem cells populations expressing CD44 and other stem cell markers},
author = {Kholoud Alwosaibai and Salmah Aalmri and Miral Mashhour and Salim Ghandorah and Abdulraheem Alshangiti and Faisal Azam and Waleed Selwi and Lubna Gharaibeh and Yasser Alatawi and Zainab Alruwaii and Hashem O. Alsaab },
url = {https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10404-x},
doi = {10.1186/s12885-022-10404-x},
issn = {1471-2407},
year = {2023},
date = {2023-01-05},
urldate = {2023-01-05},
journal = {BMC Cancer},
number = {13},
pages = {16},
abstract = {Background
Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer.
Methods
A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients’ medical record to investigate the association with PD-L1, TILs, and stem cells expressions.
Results
We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5.
Conclusions
PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer.
Methods
A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients’ medical record to investigate the association with PD-L1, TILs, and stem cells expressions.
Results
We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5.
Conclusions
PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.
Krigers, Aleksandrs; Moser, Patrizia; Fritsch, Helga; Demetz, Matthias; Kerschbaumer, Johannes; Brawanski, Konstantin R.; Thomé, Claudius; Freyschlag, Christian F.
M8 Microscope and Scanner Helps Understand the Role of Connexin-43 and Ki67 in Mon-glial Central Nervous System Tumors
Intercellular communication mediated by gap junctions plays an important role in the exchange of small molecules and ions, which not only serve to maintain homeostasis but also affect cell proliferation and differentiation. The protein connexin-43 (Cx43) is involved in the formation of these gap junctional channels and hemichannels. To better understand this, researchers examined the expression of Cx43 and Ki67 in formalin-fixed, paraffin-embedded samples of human brain metastases, meningiomas and neurinomas using immunohistochemistry. To comprehensively understand the functions of connexin-43 and Ki67 within non-glial central nervous system tumors, researchers used PreciPoint’s M8 digital microscope and scanner.
Result: Researchers used our M8 Microscope and Scanner in multiple instances. M8 Microscope and Scanner 200x magnification helped researchers to understand why metastases from NSCLC did not express Cx43 as opposed to the affected cortex. Additionally, samples under M8 showed that the cellular nuclei remain unstained.
@article{nokey,
title = {The relationship between connexin-43 expression and Ki67 in non-glial central nervous system tumors},
author = {Aleksandrs Krigers and Patrizia Moser and Helga Fritsch and Matthias Demetz and Johannes Kerschbaumer and Konstantin R. Brawanski and Claudius Thomé and Christian F. Freyschlag},
url = {https://journals.sagepub.com/doi/full/10.1177/03936155221143138},
doi = {10.1177/03936155221143138},
year = {2023},
date = {2023-01-01},
urldate = {2023-01-01},
journal = {Sage Journals},
volume = {38},
issue = {1},
abstract = {“Background
Advanced intercellular communication is a known oncogenic factor. In the central nervous system, Connexin-43 (Cx43) forms this junctional networking. Moreover, it correlates with the proliferation rate, and thus behavior, of gliomas. We assessed the expression of Cx43 and its relationship to Ki67 in other common central nervous system tumors.
…
Results
A total of 14 metastases of different extracerebral carcinomas, 6 meningiomas, and 10 neurinomas were evaluated. Five (36%) metastases and 5 (31%) meningiomas/neurinomas showed minor expression, whereas 6 (43%) metastases and 2 (13%) meningiomas/neurinomas showed no Cx43 expression at all. In 3 (21%) metastases and 9 (56%) meningiomas/neurinomas, moderate or strong expression of Cx43 was identified. The higher expression of Cx43 in meningiomas and neurinomas directly correlated with Ki67, r = 0.53 (P = 0.034). For metastases no significant correlation was found. Mitotic index in meningiomas/neurinomas correlated with Ki67 expression, r = 0.74 (P < 0.001), but did not show statistically significant correlation with Cx43 expression in these tumors.
Conclusions
The expression of Cx43 as a marker of cell-to-cell networking exposed a significant correlation with the Ki67-defined proliferation index in case of primary central nervous system neuroectodermal neoplasms. However, it does not seem to play a comparable role in metastases with extracerebral origin.”
},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Advanced intercellular communication is a known oncogenic factor. In the central nervous system, Connexin-43 (Cx43) forms this junctional networking. Moreover, it correlates with the proliferation rate, and thus behavior, of gliomas. We assessed the expression of Cx43 and its relationship to Ki67 in other common central nervous system tumors.
…
Results
A total of 14 metastases of different extracerebral carcinomas, 6 meningiomas, and 10 neurinomas were evaluated. Five (36%) metastases and 5 (31%) meningiomas/neurinomas showed minor expression, whereas 6 (43%) metastases and 2 (13%) meningiomas/neurinomas showed no Cx43 expression at all. In 3 (21%) metastases and 9 (56%) meningiomas/neurinomas, moderate or strong expression of Cx43 was identified. The higher expression of Cx43 in meningiomas and neurinomas directly correlated with Ki67, r = 0.53 (P = 0.034). For metastases no significant correlation was found. Mitotic index in meningiomas/neurinomas correlated with Ki67 expression, r = 0.74 (P < 0.001), but did not show statistically significant correlation with Cx43 expression in these tumors.
Conclusions
The expression of Cx43 as a marker of cell-to-cell networking exposed a significant correlation with the Ki67-defined proliferation index in case of primary central nervous system neuroectodermal neoplasms. However, it does not seem to play a comparable role in metastases with extracerebral origin.”
Kono, Yosuke; Yokota, Shigefumi; Fukushi, Isato; Arima, Yosuke; Onimaru, Hiroshi; Okazaki, Shuntaro; Takeda, Kotaro; Yazawa, Itaru; Yoshizawa, Masashi; Hasebe, Yohei; Koizumi, Keiichi; Pokorski, Mieczyslaw; Toda, Takako; Sugita, Kanji; Okada, Yasumasa
Digital microscope and M8 slidescanner in use in brain research
As the control element and processing unit for information, the brain is one of the most important organs in humans. Because it is so complex, many processes in the brain are still unexplored. In their scientific report “Structural and functional connectivity from the dorsomedial hypothalamus to the ventral medulla as a chronological amplifier of sympathetic outflow”, published in the scientific journal Nature, Yosuke Kono et al. investigate the structural and functional connection of the dorsomedial hypothalamus, an area in the forebrain, and the ventral medulla, which is located in the rhomboid brain. Here, the structures of rat brains were studied as a model organism. Measurements were made by tractography, a method to visualize particle fluxes in the cells by color, and by voltage-dependent dyes, which can visualize the membrane potential in the neurons by color. Our M8 microscope was used to scan the tissue sections on which the tractography was subsequently performed.
Result: Our M8 microscope was used to scan the tissue sections on which tractography was subsequently performed.
@article{nokey,
title = {Structural and functional connectivity from the dorsomedial hypothalamus to the ventral medulla as a chronological amplifier of sympathetic outflow},
author = {Yosuke Kono and Shigefumi Yokota and Isato Fukushi and Yosuke Arima and Hiroshi Onimaru and Shuntaro Okazaki and Kotaro Takeda and Itaru Yazawa and Masashi Yoshizawa and Yohei Hasebe and Keiichi Koizumi and Mieczyslaw Pokorski and Takako Toda and Kanji Sugita and Yasumasa Okada },
url = {https://www.nature.com/articles/s41598-020-70234-4},
doi = {10.1038/s41598-020-70234-4},
year = {2022},
date = {2022-08-07},
journal = {Scientific Reports},
volume = {10},
issue = {13325},
abstract = {Psychological stress activates the hypothalamus, augments the sympathetic nervous output, and elevates blood pressure via excitation of the ventral medullary cardiovascular regions. However, anatomical and functional connectivity from the hypothalamus to the ventral medullary cardiovascular regions has not been fully elucidated. We investigated this issue by tract-tracing and functional imaging in rats. Retrograde tracing revealed the rostral ventrolateral medulla was innervated by neurons in the ipsilateral dorsomedial hypothalamus (DMH). Anterograde tracing showed DMH neurons projected to the ventral medullary cardiovascular regions with axon terminals in contiguity with tyrosine hydroxylase-immunoreactive neurons. By voltage-sensitive dye imaging, dynamics of ventral medullary activation evoked by electrical stimulation of the DMH were analyzed in the diencephalon-lower brainstem-spinal cord preparation of rats. Although the activation of the ventral medulla induced by single pulse stimulation of the DMH was brief, tetanic stimulation caused activation of the DMH sustained into the post-stimulus phase, resulting in delayed recovery. We suggest that prolonged excitation of the DMH, which is triggered by tetanic electrical stimulation and could also be triggered by psychological stress in a real life, induces further prolonged excitation of the medullary cardiovascular networks, and could contribute to the pathological elevation of blood pressure. The connectivity from the DMH to the medullary cardiovascular networks serves as a chronological amplifer of stress-induced sympathetic excitation. This notion will be the anatomical and pathophysiological basis to understand the mechanisms of stress-induced sustained augmentation of sympathetic activity.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Mowday, Alexandra M.; Dubois, Ludwig J.; Kubiak, Aleksandra M.; Chan-Hyams, Jasmine V. E.; Guise, Christopher P.; Ashoorzadeh, Amir; Lambin, Philippe; Ackerley, David F.; Smaill, Jeff B.; Minton, Nigel P.; Theys, Jan; Patterson, Adam V.
Advancing Cancer Treatment: The M8 Microscope in Investigating Tumor-Proximate Gene Therapeutics via Clostridia
Today, medicine offers a wide variety of approaches to the treatment of cancer. Some of them are already used as standard, others are still in research, but are quite promising. In their study, Mowday et al. describe one of these research approaches in which the bacterium Clostridium sporogenes is used to effect a cure. In “Use of an optimized enzyme/prodrug combination for Clostridia directed enzyme prodrug therapy induces a significant growth delay in necrotic tumors” the bacterium is cultivated in the direct environment of the tumor tissue and is supposed to produce a therapeutic gene there. This is possible because the tumor tissue forms a nutrient environment that is selective for Clostridium sporogenes and thus promotes growth.
Result: Our digital microscope was used for the scanning tumor tissue sections that were stained with hematoxylin eosin or Gram-twort.
@mastersthesis{nokey,
title = {Use of an optimised enzyme/prodrug combination for Clostridia directed enzyme prodrug therapy induces a significant growth delay in necrotic tumours},
author = {Alexandra M. Mowday and Ludwig J. Dubois and Aleksandra M. Kubiak and Jasmine V. E. Chan-Hyams and Christopher P. Guise and Amir Ashoorzadeh and Philippe Lambin and David F. Ackerley and Jeff B. Smaill and Nigel P. Minton and Jan Theys and Adam V. Patterson },
url = {https://www.nature.com/articles/s41417-021-00296-7},
doi = {10.1038/s41417-021-00296-7},
year = {2021},
date = {2021-02-08},
journal = {Cancer Gene Therapy},
volume = {29},
pages = {178-188},
abstract = {Necrosis is a typical histological feature of solid tumours that provides a selective environment for growth of the nonpathogenic anaerobic bacterium Clostridium sporogenes. Modest anti-tumour activity as a single agent encouraged the use of C. sporogenes as a vector to express therapeutic genes selectively in tumour tissue, a concept termed Clostridium Directed Enzyme Prodrug Therapy (CDEPT). Here, we examine the ability of a recently identified Neisseria meningitidis type I nitroreductase (NmeNTR) to metabolise the prodrug PR-104A in an in vivo model of CDEPT. Human HCT116 colon cancer cells stably over-expressing NmeNTR demonstrated significant sensitivity to PR-104A, the imaging agent EF5, and several nitro(hetero)cyclic anti-infective compounds. Chemical induction of necrosis in human H1299 xenografts by the vascular disrupting agent vadimezan promoted colonisation by NmeNTR-expressing C. sporogenes, and efficacy studies demonstrated moderate but significant anti-tumour activity of spores when compared to untreated controls. Inclusion of the pre-prodrug PR-104 into the treatment schedule provided significant additional activity, indicating proof-of-principle. Successful preclinical evaluation of a transferable gene that enables metabolism of both PET imaging agents (for vector visualisation) and prodrugs (for conditional enhancement of efficacy) is an important step towards the prospect of CDEPT entering clinical evaluation.},
keywords = {M8},
pubstate = {published},
tppubtype = {mastersthesis}
}
Klatt, Wybke; Wallner, Susanne; Brochhausen, Christoph; Stolwijk, Judith A.; Schreml, Stephan
Decoding Skin Tumors: Proton-Sensing G-Protein Coupled Receptors and the Vital Role of the M8 Microscope
The cases of skin cancer in Germany had been rising since the last few decades and regarding a report of the health insurance company TK, every third diagnosed tumor is a skin tumor. Because of that, continuous medical research is important to understand the mechanism of tumor proliferation. This interesting topic is also investigated in the scientific paper of Klatt W., Wallner S., Brochhausen C. et al. „Expression profiles of proton‑sensing G‑protein coupled receptors in common skin tumors “. In this research, our microscope M8 was used for whole slide scanning of immunohistochemically stained tissue.
Result: Our digital scanner was not only used for generating the scans as also for analyzing the pictures with our viewer-software Viewpoint. We are proud that our product could support this research.
@article{nokey,
title = {Expression profiles of proton‑sensing G‑protein coupled receptors in common skin tumors},
author = {Wybke Klatt and Susanne Wallner and Christoph Brochhausen and Judith A. Stolwijk and Stephan Schreml},
url = {https://www.nature.com/articles/s41598-020-71700-9},
doi = {10.1038/s41598-020-71700-9},
year = {2020},
date = {2020-09-18},
urldate = {2020-09-18},
journal = {Scientific Reports},
volume = {10},
issue = {15327},
abstract = {The proton-sensing GPCRs (pH-GPCRs) GPR4 (GPR19), TDAG8 (GPR65, T-cell death associated gene 8), OGR1 (GPR68, ovarian cancer GPCR1), and G2A (GPR132, G2 accumulation protein) are involved in sensing and transducing changes in extracellular pH (pHe). Extracellular acidification is a central hallmark of solid cancer. pH-GPCR function has been associated with cancer cell proliferation, adhesion, migration and metastasis, as well as with modulation of the immune system. Little is known about the expression levels and role of pH-GPCRs in skin cancer. To better understand the functions of pH-GPCRs in skin cancer in vivo, we examined the expression-profiles of GPR4, TDAG8, OGR1 and G2A in four common skin tumors, i.e. squamous cell carcinoma (SCC), malignant melanoma (MM), compound nevus cell nevi (NCN), basal cell carcinoma (BCC). We performed immunohistochemistry and immunofluorescence staining on paraffin-embedded tissue samples acquired from patients suffering from SCC, MM, NCN or BCC. We show the expression of pH-GPCRs in four common skin cancers. Different expression patterns in the investigated skin cancer types indicate that the different pH-GPCRs may have distinct functions in tumor progression and serve as novel therapeutic targets.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Seo, Jincheol; Park, Junghyung; Kim, Keonwoo; Won, Jinyoung; Yeo, Hyeon-Gu; Jin, Yeung Bae; Koo, Bon-Sang; Lim, Kyung Seob; Jeong, Kang-Jin; Kang, Philyong; Lee, Hwal-Yong; Choi, Won Seok; Baek, Seung Ho; Jeon, Chang-Yeop; Hong, Jung-Joo; Huh, Jae-Won; Kim, Young-Hyun; Park, Sang Je; Kim, Sun-Uk; Lee, Dong-Seok; Lee, Youngjeon
Researching Parkinson\'s disease using the M8 digital microscope and slide scanner
As the second most common neurodegenerative disease and 200000 deaths in 2018, Parkinson’s is one of the most insidious diseases of the 21st century. Research on the disease is ongoing throughout for better diagnoses and treatment options. Jincheol Seo et al, in their Research Article “Chronic Infiltration of T Lymphocytes into the Brain in a Non-human Primate Model of Parkinson’s Disease”of the Neuroscience of the IBR (International Brain Research Organization), describe the influence of T lymphocytes on the degeneration of neurons in the brain. As a model organism, the studies were conducted in Macaca fascicularis, Javanese monkeys.
Result: Tissue sections of the brain were immunohistochemically stained and scanned with our M8.
@mastersthesis{nokey,
title = {Chronic Infiltration of T Lymphocytes into the Brain in a Non-human Primate Model of Parkinson’s Disease},
author = {Jincheol Seo and Junghyung Park and Keonwoo Kim and Jinyoung Won and Hyeon-Gu Yeo and Yeung Bae Jin and Bon-Sang Koo and Kyung Seob Lim and Kang-Jin Jeong and Philyong Kang and Hwal-Yong Lee and Won Seok Choi and Seung Ho Baek and Chang-Yeop Jeon and Jung-Joo Hong and Jae-Won Huh and Young-Hyun Kim and Sang Je Park and Sun-Uk Kim and Dong-Seok Lee and Youngjeon Lee},
url = {https://www.sciencedirect.com/science/article/pii/S0306452220300737?via%3Dihub},
doi = {10.1016/j.neuroscience.2020.01.043},
year = {2020},
date = {2020-04-01},
journal = {Neuroscience},
volume = {431},
pages = {73-85},
abstract = {Study of interactions between the nervous system and immunity offers insights into the pathogenesis of Parkinson’s disease (PD) and potential therapeutic strategies for neurodegenerative diseases. Studies on rodents have revealed regulatory mechanisms of microglial activation and T lymphocyte recruitment in PD. However, the mechanisms underlying chronic T lymphocyte infiltration into the brain after 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) injection into a non-human primate (NHP) model of PD remain unknown. This study aimed to investigate changes in serum RANTES (regulated on activation, normal T cell expression and secretion) and analyze the chronic infiltration of T lymphocytes into the brain and microglia activation in NHPs at 48 weeks post-MPTP administration. We found selective and local chronic infiltration of CD4+ and CD8+ T lymphocytes, loss of dopaminergic neurons, dopamine transporter expression, chronic normalization of RANTES in the peripheral blood, and altered microglial morphology at 48 weeks after MPTP injection. This study confirms the involvement of CD4+ and CD8+ T lymphocyte infiltration in MPTP-induced NHP models of PD. Additionally, we corroborated previous findings regarding the mechanisms of T lymphocyte-induced neurodegeneration. The findings of chronic infiltration of T lymphocytes in our NHP model of PD provide novel insights into PD pathogenesis and the development of preventive and therapeutic agents.},
keywords = {M8},
pubstate = {published},
tppubtype = {mastersthesis}
}
Heckmann, L; Langenstroth-Röwer, D; Wistuba, J; Portela, J M D; van Pelt, A M M; Redmann, K; Stukenborg, J B; Schlatt, S; Neuhaus, N
Digital microscope and M8 slidescanner in use for reproductive medicine research
Reproductive medicine is an important scientific topic, as it can offer help in cases of unwanted childlessness. In the study of Heckmann et al. „The initial maturation status of marmoset testicular tissues has an impact on germ cell maintenance and somatic cell response in tissue fragment culture”, our microscope helped to generate scans of testicular tissue to make certain types of cell morphologies visible.
Result: Our digital microscope was used for scanning the cell structures that were colored immunohistochemical and have a direct impact on the fertility of an individual. We are proud that our microscope is part of this paper and hope that it will also find use in some following research.
@article{nokey,
title = {The initial maturation status of marmoset testicular tissues has an impact on germ cell maintenance and somatic cell response in tissue fragment culture},
author = {L Heckmann and D Langenstroth-Röwer and J Wistuba and J M D Portela and A M M van Pelt and K Redmann and J B Stukenborg and S Schlatt and N Neuhaus },
url = {https://academic.oup.com/molehr/article/26/6/374/5814289?login=false},
doi = {10.1093/molehr/gaaa024},
year = {2020},
date = {2020-04-01},
urldate = {2020-04-01},
journal = {Molecular Human Reproduction},
volume = {26},
issue = {6},
pages = {374-388},
abstract = {Successful in vitro spermatogenesis was reported using immature mouse testicular tissues in a fragment culture approach, raising hopes that this method could also be applied for fertility preservation in humans. Although maintaining immature human testicular tissue fragments in culture is feasible for an extended period, it remains unknown whether germ cell survival and the somatic cell response depend on the differentiation status of the tissue. Employing the marmoset monkey (Callithrix jacchus), we aimed to assess whether the maturation status of prepubertal and peri-/pubertal testicular tissues influence the outcome of testis fragment culture. Testicular tissue fragments from 4- and 8-month-old (n =3, each) marmosets were cultured and evaluated after 0, 7, 14, 28, and 42 days. Immunohistochemistry was performed for identification and quantification of germ cells (melanoma-associated antigen 4) and Sertoli cell maturation status (anti-Müllerian hormone: AMH). During testis fragment culture, spermatogonial numbers were significantly reduced (P <0.05) in the 4- but not 8-month-old monkeys, at Day 0 versus Day 42 of culture. Moreover, while Sertoli cells from 4-month-old monkeys maintained an immature phenotype (i.e. AMH expression) during culture, AMH expression was regained in two of the 8-month-old monkeys. Interestingly, the progression of differentiation to the later meiotic stage was solely observed in one 8-month-old marmoset, which was at an intermediate state regarding germ cell content, with gonocytes as well as spermatocytes present, as well as Sertoli cell maturation status. Although species-specific differences might influence the outcome of testis fragment experiments in vitro, our study demonstrated that the developmental status of the testicular tissues needs to be considered as it seems to be decisive for germ cell maintenance, somatic cell response and possibly the differentiation potential.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Portela, Joana M. D.; Heckmann, Laura; Wistuba, Joachim; Sansone, Andrea; van Pelt, Ans M. M.; Kliesch, Sabine; Schlatt, Stefan; Neuhaus, Nina
Digital microscope and slidescanner M8 in use for cancer research
Microscopy is a conventional method for experimental tests and the optical analysis of cell morphology and changes in molecular expression. As so, our M8 is used in some of these publications. Portela J., Heckmann L, Wistuba J. et al. also published a research paper with the title „Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues” where our M8 found a use.
Result: Our digital microscope was used for scanning testicular tissue sections that were stained histochemically and immunohistochemically. We are proud that our microscope is part of this paper and hope that it will also find use in some following research.
@article{nokey,
title = {Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues},
author = {Joana M. D. Portela and Laura Heckmann and Joachim Wistuba and Andrea Sansone and Ans M. M. van Pelt and Sabine Kliesch and Stefan Schlatt and Nina Neuhaus},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019285/},
doi = {10.3390/jcm9010224},
year = {2020},
date = {2020-01-14},
urldate = {2020-01-14},
journal = {Journal of Clinical Medicine},
volume = {9},
number = {224},
issue = {1},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}
Matek, Christian; Schwarz, Simone; Spiekermann, Karsten; Marr, Carsten
Revolutionizing Leukemia Diagnosis: The Critical Role of O8 Oil Microscope in AI-Assisted Blast Cell Recognition
The reliable diagnosis of myeloid leukaemia by identifying blast cells in peripheral blood is currently still a very complicated process. The identification is carried out entirely analogously, by well-trained technical staff and doctors. On the one hand, this is precisely why the error rate is very low; on the other hand, it is not possible to define standardised procedures that would be very helpful for routine processes. In addition, the purely analogue process is very time-consuming and monotonous and therefore very tiring.
Result: One of the results of the study that we want to mention because it also plays an important role for our product O8 is the so-called saliency map. This representation visualises how important certain pixels on an image were for the analysis. In figure 1 you can see that the areas where the cells are visible in the colour image were clearly more relevant for the analysis. Thus, we can say that on the one hand the network resulted in a very specific and good recognition of the cells, but also that the scanner was able to provide high-quality images for the recognition. In addition, the good networking of our software with further interfaces for the transfer of the scanner data into the basic CNN structure offered a safe and simple further processing of the images.
@article{nokey,
title = {Human-level recognition of blast cells in acute myeloid leukaemia with convolutional neural networks.},
author = {Christian Matek and Simone Schwarz and Karsten Spiekermann and Carsten Marr },
url = {https://www.nature.com/articles/s42256-019-0101-9},
doi = {10.1038/s42256-019-0101-9},
year = {2019},
date = {2019-11-12},
urldate = {2019-11-12},
journal = {Nature Machine Intelligence},
issue = {1},
pages = {538-544},
abstract = {Reliable recognition of malignant white blood cells is a key step in the diagnosis of haematologic malignancies such as acute myeloid leukaemia. Microscopic morphological examination of blood cells is usually performed by trained human examiners, making the process tedious, time-consuming and hard to standardize. Here, we compile an annotated image dataset of over 18,000 white blood cells, use it to train a convolutional neural network for leukocyte classification and evaluate the network’s performance by comparing to inter- and intra-expert variability. The network classifies the most important cell types with high accuracy. It also allows us to decide two clinically relevant questions with human-level performance: (1) if a given cell has blast character and (2) if it belongs to the cell types normally present in non-pathological blood smears. Our approach holds the potential to be used as a classification aid for examining much larger numbers of cells in a smear than can usually be done by a human expert. This will allow clinicians to recognize malignant cell populations with lower prevalence at an earlier stage of the disease.},
keywords = {O8},
pubstate = {published},
tppubtype = {article}
}
Park, Junghyung; Seo, Jincheol; Won, Jinyoung; Yeo, Hyeon-Gu; Ahn, Yu-Jin; Kim, Keonwoo; Jin, Yeung Bae; Koo, Bon-Sang; Lim, Kyung Seob; Jeong, Kang-Jin; Kang, Philyong; Lee, Hwal-Yong; Baek, Seung Ho; Jeon, Chang-Yeop; Hong, Jung-Joo; Huh, Jae-Won; Kim, Young-Hyun; Park, Sang-Je; Kim, Sun-Uk; Lee, Dong-Seok; Lee, Sang-Rae; Lee, Youngjeon
Digital microscope and M8 slidescanner in use for research into neurodegenerative diseases
According to a report of The Lancet Neurology of May 2019 neurological disorders is with 9,0 million deaths and 16,5% of global deaths, the second leading cause of death after heart disease and with 276 million DALYs and 11,6% of global DALYs, it is the leading cause of disability. In the scientific paper “Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson’s Disease: Drp1 and CDK5/p25 Signaling” Park J. et al examining abnormal Mitochondria of non-human primate and the impact of it on Parkinson disease.
Result: Our digital scanner M8 was used to generate the scans of tissue sections with the immunohistochemically stained mitochondria.
@article{nokey,
title = {Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling},
author = {Junghyung Park and Jincheol Seo and Jinyoung Won and Hyeon-Gu Yeo and Yu-Jin Ahn and Keonwoo Kim and Yeung Bae Jin and Bon-Sang Koo and Kyung Seob Lim and Kang-Jin Jeong and Philyong Kang and Hwal-Yong Lee and Seung Ho Baek and Chang-Yeop Jeon and Jung-Joo Hong and Jae-Won Huh and Young-Hyun Kim and Sang-Je Park and Sun-Uk Kim and Dong-Seok Lee and Sang-Rae Lee and Youngjeon Lee},
url = {https://pubmed.ncbi.nlm.nih.gov/31308800/},
doi = {10.5607/en.2019.28.3.414},
year = {2019},
date = {2019-05-24},
journal = {Experimental Neurobiology},
volume = {28},
issue = {3},
pages = {414-424},
abstract = {Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson’s disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.},
keywords = {M8},
pubstate = {published},
tppubtype = {article}
}