Fully automated segmentation and morphometrical analysis of muscle fiber images

Kim, Yoo-Jin; Brox, Thomas; Feiden, W.; Weickert, Joachim

doi:10.1002/cyto.a.20334

Cited by 42 publications

(35 citation statements)

References 19 publications

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“…The presence of sub-G1 peaks on DNA content histograms is generally accepted to represent apoptotic cells (20). As cell cycle analysis demonstrated that combined pitavastatin-DTIC treatment resulted in sub-G1 peaks ( Fig.…”

Section: Combined Pitavastatin and Dtic Treatment Induces G1 Cell Cycmentioning

confidence: 99%

Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells

Al-Qatati

Aliwaini

2017

Oncol Lett

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Abstract. Melanoma is an aggressive skin cancer and its incidence is increasing faster than any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy for metastatic melanoma, it has limited success. Statins, including pitavastatin, have been demonstrated to have a range of anticancer effects in a number of human cancer cell lines. The present study therefore explored the anti-cancer activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma cells. Cell survival assays demonstrated that combined DTIC and pitavastatin treatment resulted in synergistic cell death. Cell cycle analyses further revealed that this combined treatment resulted in a G1 cell cycle arrest, as well as a sub-G1 population, indicative of apoptosis. Activation of apoptosis was confirmed by Annexin V-fluorescein isothiocyanate/propidium iodide double-staining and an increase in the levels of active caspase 3 and cleaved poly (ADP-ribose) polymerase. Furthermore, it was demonstrated that apoptosis occurs through the intrinsic pathway, evident from the release of cytochrome c. Finally, combined DTIC and pitavastatin treatment was demonstrated to also activate autophagy as part of a cell death mechanism. The present study provides novel evidence to suggest that the combined treatment of DTIC and pitavastatin may be effective in the treatment of melanoma. IntroductionMelanoma is a particularly aggressive skin cancer and its incidence is increasing faster than any other cancer worldwide (1). At present, the 10-year survival rate of patients diagnosed with advanced (stage IV) metastatic melanoma is <10% (2), which highlights the importance of early detection and treatment. The Food and Drug Administration approved the chemotherapeutic agent dacarbazine (DTIC) for the treatment of metastatic melanoma in 1975, and it remains the only licensed chemotherapeutic agent in use today (1). DTIC is a methylating agent which causes DNA damage, cell cycle arrest and apoptosis. Despite this, only 2% of all patients with metastatic melanoma receiving this treatment demonstrate a significant response and only 11.2% demonstrate a partial response (3). Resistance to DTIC has been associated with the upregulation of pro-survival signals and anti-apoptotic molecules in cancer cells. Despite its moderate effects, DTIC continues to be the standard treatment for metastatic melanoma as no other chemotherapeutic treatment has been demonstrated to have a significantly increased chance of survival when compared with DTIC (4,5). Provided the limited efficacy of the current metastatic melanoma chemotherapies in addition to the increasing incidence of melanoma cases, there appears to be a need for the development of more effective treatment strategies.Statins are a group of drugs commonly used for the reduction of cholesterol levels (6). They work by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, a critical enzyme in the mevalonate pathway, which is responsible for cholesterol synthesis (6,7). In addition, statins have been de...

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Section: Combined Pitavastatin and Dtic Treatment Induces G1 Cell Cycmentioning

confidence: 99%

Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells

Al-Qatati

Aliwaini

2017

Oncol Lett

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“…To the best of our knowledge, this is the largest and most comprehensive dataset of images analyzed in a neuromuscular study. Previous reports have been published of attempts to facilitate the automated extraction of geometric characteristics from muscle biopsies [11][12][13][14][15][16]. These studies rely on the development of segmentation methods using a very small number of samples to only extract morphometric information.…”

Section: Discussionmentioning

confidence: 99%

“…However, it was surprising that the 'degree of neighbors' was more important than features related to the shape of the fibers. Interestingly, none of the previous characteristics (15,18,19) were selected when control and NA (12,20,21,22) were compared. The three network characteristics selected are related to the organization of the fiber types and were able to capture the characteristic fibertype grouping due to secondary reinnervation events.…”

Section: Discussionmentioning

confidence: 99%

“…A large panel of different histochemical and histoenzymatic techniques are necessary to identify pathologic changes in the routine diagnostic process [9,10] (Additional file 1: Figure S1). Previous attempts to automate the extraction of geometrical characteristics from normal muscle biopsies have been published [11][12][13][14][15][16], but those methods fail to provide an automated analysis or adequate scrutiny of the information derived from the analysis. Our analysis begins at this point, taking into account a large number of samples to study both geometrical and network data to include morphometric and organizational information.…”

Section: Introductionmentioning

confidence: 99%

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Quantifiable diagnosis of neuromuscular diseases through network analysis

Rivas¹,

Sáez²,

Montero-Sánchez³

et al. 2015

Neuromuscular Disorders

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Background: The diagnosis of neuromuscular diseases is strongly based on the histological characterization of muscle biopsies. However, this morphological analysis is mostly a subjective process and difficult to quantify. We have tested if network science can provide a novel framework to extract useful information from muscle biopsies, developing a novel method that analyzes muscle samples in an objective, automated, fast and precise manner.

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“…In the literature, there are several publications on automatic detection and classification of nuclei and FISH analysis on fluorescent images (35)(36)(37) and complex automated segmentation methods for membrane and muscle fiber for example (31,38).…”

Section: Quantitative Imagingmentioning

confidence: 99%

Automated multichannel fluorescent whole slide imaging and its application for cytometry

Varga¹,

Ficsor²,

Kamaras³

et al. 2009

Cytometry Pt A

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Slide-based image cytometry (SBC) has several advantages over flow cytometry but it is not widely used because of its low throughput, complicated workflow, and high price. Fully automated microscopes became affordable with the advent of whole slide imaging (WSI) and they can be transformed into a cytometer. A MIRAX MIDI automated whole slide imager was used with metal-halide and light emitting diode (LED)-based fluorescent illumination, filter block changer, and a cooled monochrome charge coupled device camera. The MIRAX control software was further developed for fluorescent sample detection, autofocusing, multichannel digitization, and signal correction due to nonuniform illumination. Fluorescent calibration beads were used to verify the linearity of the system. The HistoQuant software package of the MIRAX viewer was used for image segmentation and quantitative analysis. The data was displayed by the histogram, scatter plot, and gallery functions of the same program. Fluorescent samples can be reliably detected, focused, and scanned. The measured integrated fluorescence showed linearity with exposure time and staining intensity. Automated fluorescent WSI with stable LED illumination and high-quality homogeneous fluorescent slides can be used conveniently for SBC. ' 2009 International Society for Advancement of Cytometry

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Fully automated segmentation and morphometrical analysis of muscle fiber images

Cited by 42 publications

References 19 publications

Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells

Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells

Quantifiable diagnosis of neuromuscular diseases through network analysis

Automated multichannel fluorescent whole slide imaging and its application for cytometry

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