Unveiling Cancer Metabolism through Spontaneous and Coherent Raman Spectroscopy and Stable Isotope Probing

Xu, Jiabao; Tong, Yu; Zois, Christos E.; Cheng, Ji‐Xin; Tang, Yuguo; Harris, Adrian L.; Huang, Wei E.

doi:10.3390/cancers13071718

Cited by 49 publications

(39 citation statements)

References 161 publications

(215 reference statements)

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“…There are many advantages of Raman spectroscopy that justify its successful implementation into cancer cell profiling for routine clinical pathology practice and live-cell imaging. In addition to the high sensitivity and chemical specificity, using minimal or no sample pretreatment, small sample volume, and the possibility to perform measurements in liquids, Raman imaging allows nondestructive, intrinsic, and label-free cell characterization with excellent spatial resolution [4,10]. This great potential of RS for non-invasive cancer diagnostics has been effectively tested in a wide range of solid tumors, including breast, skin, brain, lung cancers, and others [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Towards Raman-Based Screening of Acute Lymphoblastic Leukemia-Type B (B-ALL) Subtypes

Leszczenko

Borek-Dorosz

Nowakowska

et al. 2021

Cancers

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Acute lymphoblastic leukemia (ALL) is the most common type of malignant neoplasms in the pediatric population. B-cell precursor ALLs (BCP-ALLs) are derived from the progenitors of B lymphocytes. Traditionally, risk factors stratifying therapy in ALL patients included age at diagnosis, initial leukocytosis, and the response to chemotherapy. Currently, treatment intensity is modified according to the presence of specific gene alterations in the leukemic genome. Raman imaging is a promising diagnostic tool, which enables the molecular characterization of cells and differentiation of subtypes of leukemia in clinical samples. This study aimed to characterize and distinguish cells isolated from the bone marrow of patients suffering from three subtypes of BCP-ALL, defined by gene rearrangements, i.e., BCR-ABL1 (Philadelphia-positive, t(9;22)), TEL-AML1 (t(12;21)) and TCF3-PBX1 (t(1;19)), using single-cell Raman imaging combined with multivariate statistical analysis. Spectra collected from clinical samples were compared with single-cell spectra of B-cells collected from healthy donors, constituting the control group. We demonstrated that Raman spectra of normal B cells strongly differ from spectra of their malignant counterparts, especially in the intensity of bands, which can be assigned to nucleic acids. We also showed that the identification of leukemia subtypes could be automated with the use of chemometric methods. Results prove the clinical suitability of Raman imaging for the identification of spectroscopic markers characterizing leukemia cells.

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Section: Introductionmentioning

confidence: 99%

Towards Raman-Based Screening of Acute Lymphoblastic Leukemia-Type B (B-ALL) Subtypes

Leszczenko

Borek-Dorosz

Nowakowska

et al. 2021

Cancers

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“…The SCRS of H3 presents a distinct Raman band at 1735 cm –1 , contributed by the CO ester stretching of PHA . PHA is composed of hydroxyl fatty acids stored as lipid inclusions.…”

Section: Resultsmentioning

confidence: 99%

“…The SCRS of H3 presents a distinct Raman band at 1735 cm −1 , contributed by the CO ester stretching of PHA. 28 PHA is composed of hydroxyl fatty acids stored as lipid inclusions. When carbon and energy are needed, the intracellular PHA is usually depolymerized into D(−)hydroxybutyric acid and then metabolized into acetoacetate and acetoacetyl-CoA.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Classification and Identification of Archaea Using Single-Cell Raman Ejection and Artificial Intelligence: Implications for Investigating Uncultivated Microorganisms

Wang

Cui

et al. 2021

Anal. Chem.

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Archaea can produce special cellular components such as polyhydroxyalkanoates, carotenoids, rhodopsin, and ether lipids, which have valuable applications in medicine and green energy production. Most of the archaeal species are uncultivated, posing challenges to investigating their biomarker components and biochemical properties. In this study, we applied Raman spectroscopy to examine the biological characteristics of nine archaeal isolates, including halophilic archaea (Haloferax larsenii, Haloarcula argentinensis, Haloferax mediterranei, Halomicrobium mukohataei, Halomicrobium salinus, Halorussus sp., Natrinema gari), thermophilic archaea (Sulfolobus acidocaldarius), and marine group I (MGI) archaea (Nitrosopumilus maritimus). Linear discriminant analysis of the Raman spectra allowed visualization of significant separations among the nine archaeal isolates. Machine-learning classification models based on support vector machine achieved accuracies of 88−100% when classifying the nine archaeal species. The predicted results were validated by DNA sequencing analysis of cells isolated from the mixture by Raman-activated cell sorting. Raman spectra of uncultured archaea (MGII) were also obtained based on Raman spectroscopy and fluorescence in situ hybridization. The results combining multiple Raman-based techniques indicated that MGII may have the ability to produce lipids distinct from other archaeal species. Our study provides a valuable approach for investigating and classifying archaea, especially uncultured species, at the single-cell level.

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“…Hypoxia is also known to negatively influence treatment response to chemotherapy [ 27 ] and immunotherapy [ 20 , 28 ], as well as contributing to tumor aggressiveness [ 29 , 30 , 31 , 32 , 33 ]. A recent Special Issue in Cancers contained several original reports and contemporary review papers on the subject of tumor hypoxia [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. In this review, we will consider how thermal dose affects tumor hypoxia and, in turn, whether changes in hypoxia in response to thermoradiotherapy can influence treatment outcome.…”

Section: Introductionmentioning

confidence: 99%

Accurate Three-Dimensional Thermal Dosimetry and Assessment of Physiologic Response Are Essential for Optimizing Thermoradiotherapy

Dewhirst

Oleson

Kirkpatrick

et al. 2022

Cancers

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Numerous randomized trials have revealed that hyperthermia (HT) + radiotherapy or chemotherapy improves local tumor control, progression free and overall survival vs. radiotherapy or chemotherapy alone. Despite these successes, however, some individuals fail combination therapy; not every patient will obtain maximal benefit from HT. There are many potential reasons for failure. In this paper, we focus on how HT influences tumor hypoxia, since hypoxia negatively influences radiotherapy and chemotherapy response as well as immune surveillance. Pre-clinically, it is well established that reoxygenation of tumors in response to HT is related to the time and temperature of exposure. In most pre-clinical studies, reoxygenation occurs only during or shortly after a HT treatment. If this were the case clinically, then it would be challenging to take advantage of HT induced reoxygenation. An important question, therefore, is whether HT induced reoxygenation occurs in the clinic that is of radiobiological significance. In this review, we will discuss the influence of thermal history on reoxygenation in both human and canine cancers treated with thermoradiotherapy. Results of several clinical series show that reoxygenation is observed and persists for 24–48 h after HT. Further, reoxygenation is associated with treatment outcome in thermoradiotherapy trials as assessed by: (1) a doubling of pathologic complete response (pCR) in human soft tissue sarcomas, (2) a 14 mmHg increase in pO2 of locally advanced breast cancers achieving a clinical response vs. a 9 mmHg decrease in pO2 of locally advanced breast cancers that did not respond and (3) a significant correlation between extent of reoxygenation (as assessed by pO2 probes and hypoxia marker drug immunohistochemistry) and duration of local tumor control in canine soft tissue sarcomas. The persistence of reoxygenation out to 24–48 h post HT is distinctly different from most reported rodent studies. In these clinical series, comparison of thermal data with physiologic response shows that within the same tumor, temperatures at the higher end of the temperature distribution likely kill cells, resulting in reduced oxygen consumption rate, while lower temperatures in the same tumor improve perfusion. However, reoxygenation does not occur in all subjects, leading to significant uncertainty about the thermal–physiologic relationship. This uncertainty stems from limited knowledge about the spatiotemporal characteristics of temperature and physiologic response. We conclude with recommendations for future research with emphasis on retrieving co-registered thermal and physiologic data before and after HT in order to begin to unravel complex thermophysiologic interactions that appear to occur with thermoradiotherapy.

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Unveiling Cancer Metabolism through Spontaneous and Coherent Raman Spectroscopy and Stable Isotope Probing

Cited by 49 publications

References 161 publications

Towards Raman-Based Screening of Acute Lymphoblastic Leukemia-Type B (B-ALL) Subtypes

Towards Raman-Based Screening of Acute Lymphoblastic Leukemia-Type B (B-ALL) Subtypes

Classification and Identification of Archaea Using Single-Cell Raman Ejection and Artificial Intelligence: Implications for Investigating Uncultivated Microorganisms

Accurate Three-Dimensional Thermal Dosimetry and Assessment of Physiologic Response Are Essential for Optimizing Thermoradiotherapy

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