Abstract Objectives: Hypoxia can drive the tumor toward a more aggressive malignant phenotype through genomic and proteomic changes. Hypoxia-inducible factor-1α (HIF-1α) transactivates genes whose proteins allow metabolic adaptation to hypoxia, including carbonic anhydrase-IX (CA-IX) and glucose transporter-1 (Glut-1). This study aimed to determine whether the HIF-1α, CA-IX and Glut-1 were associated with clinico-pathological characteristics and progression-free survival in patients with cervical carcinoma. Methods: Under the written informed consent, tumor tissue samples were obtained from 54 patients with cervical carcinoma performed radical hysterectomy. The expressions of HIF-1α, CA-IX and Glut-1 were detected by immunohistochemical staining using paraffin-embedded sections. Results: CA-IX and Glut-1 expressions were found in cell membrane and cytoplasm, and HIF-1α expression was observed in cell nuclear. In 54 cases, the positive expression was observed in 28 cases for HIF-1α, 35 for CA-IX and 40 for Glut-1. The HIF-1α expression was related with clinical stage and histology, CA-IX expression was related with clinical stage, tumor size, lymph-node metastasis and lymph-vascular space involvement, and the Glut-1 expression was related with clinical stage and lymph-vascular space involvement. The multivariate regression analysis revealed that the CA-IX expression and lymph-vascular space involvement were the independent variable associated with lymph-node metastasis in patients with cervical cancer. Progression-free survival was shorter in patient with positive CA-IX expression compared to negative CA-IX expression. Conclusion: In cervical cancer patients, CA-IX expression is possible to be a risk factor for lymph-node metastasis and disease recurrence, it was suggested that pH regulation induced by CA-IX under hypoxic condition may be associated with lymph node metastasis. Citation Format: Keita Iwasaki, Hiromitsu Yabushita, Taiki Ueno, Akihiko Wakatsuki. Role of hypoxia-inducible factor-1α, carbonic anhydrase-IX and glucose transporter-1 in cervical cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4737. doi:10.1158/1538-7445.AM2014-4737
Global demand for energy is on the rise at a time when limited natural resources are fast depleting. To address this issue, microalgal biofuels are being recommended as a renewable and eco-friendly substitute for fossil fuels. Euglena gracilis is one such candidate that has received special interest due to their ability to synthesize wax esters that serve as precursors for production of drop-in jet fuel. However, to realize economic viability and achieve industrial-scale production, development of novel methods to characterize algal cells, evaluate its culture conditions, and construct appropriate genetically modified strains is necessary. Here, we report a Raman microspectroscopy-based method to visualize important metabolites such as paramylon and ester during wax ester fermentation in single Euglena gracilis cells in a label-free manner. We measured Raman spectra to obtain intracellular biomolecular information in Euglena under anaerobic condition. First, by univariate approach, we identified Raman markers corresponding to paramylon/esters and constructed their time-lapse chemical images. However, univariate analysis is severely limited in its ability to obtain detailed information as several molecules can contribute to a Raman band. Therefore, we further employed multivariate curve resolution analysis to obtain chain length-specific information and their abundance images of the produced esters. Accumulated esters in Euglena were particularly identified to be myristyl myristate (C28), a wax ester candidate suitable to prepare drop-in jet fuel. Interestingly, we found accumulation of two different forms of myristyl myristate for the first time in Euglena through our exploratory multivariate analysis. We succeeded in visualizing molecular-specific information in Euglena during wax ester fermentation by Raman microspectroscopy. It is obvious from our results that simple univariate approach is insufficient and that multivariate curve resolution analysis is crucial to extract hidden information from Raman spectra. Even though we have not measured any mutants in this study, our approach is directly applicable to other systems and is expected to deepen the knowledge on lipid metabolism in microalgae, which eventually leads to new strategies that will help to enhance biofuel production efficiency in the future.
To clarify the roles of adiponectin receptor (AdipoR) and leptin receptor (ObR) in endometrial carcinoma, the expression of AdipoR-1 and -2 and ObR in endometrial cancer was examined immunohistochemically, and correlations with clinicopathological implications were also analysed. Paraffin-embedded tissues were obtained from 77 patients with endometrial carcinoma and were stained immunohistochemically using antibodies against AdipoR-1, AdipoR-2 and ObR. AdipoR-1, AdipoR-2 and ObR were localised predominantly in the cell membrane and cytoplasm of tumour cells and normal endometrial cells. In 77 cases of endometrial cancer, positive expression was observed in 46 cases (59.7%) for AdipoR-1, 47 cases (61.0%) for AdipoR-2 and 33 cases (42.9%) for ObR. Expression of AdipoR-1 was observed most in stage I cases, G1 tumours, tumours with shallow myometrial invasion, tumours negative for lymphovascular space involvement, cases negative for adnexal invasion and cases with no lymph node metastasis. However, the expression of AdipoR-2 and ObR showed no correlation with any clinicopathological factors. Kaplan-Meier analyses revealed that progression-free and overall survival times were longer in cases with positive AdipoR-1 expression compared with negative AdipoR-1 expression. Poor expression of AdipoR-1, thus, appears to be associated with tumour grade, myometrial invasion, adnexal invasion, lymph-vascular space involvement and lymph node metastasis, as well as poor prognosis, in endometrial cancer.
In this review, historical background along with some important studies that led to the development of medical spectroscopy in Japan has been introduced. Great interest among researchers for medical applications of spectroscopy began with the development of Laser Raman spectroscopy which was then followed by the progression of FT-IR spectroscopy. Medical spectroscopy field took a quantum leap when spectrophotometers were combined with microscopes which enabled researchers to investigate at sub-cellular resolutions and acquire large number of spectra. This resulted in rapid development of suitable chemometric approaches. Some recent examples on medical applications of Raman spectroscopy and some routinely used chemometric methods such as SVD, PCA and MCR-ALS have been discussed.
The optimal treatment for profound hyponatraemia remains uncertain. Recent clinical studies have demonstrated that a standardized bolus of hypertonic saline is effective, but relying solely on this approach may not fully address the individual variability of hyponatraemia among patients. We evaluated the effectiveness of rapid bolus (RB) administration of hypertonic saline followed by predictive correction (PC) using an infusate and fluid loss formula identical to the Barsoum-Levine formula based on the Edelman equation (RB-PC) for managing profound hyponatraemia. In this retrospective observational cohort study, we evaluated 276 patients aged >18 years with s[Na] levels ≤120 mEq/L (January 2014-December 2023). Using propensity score matching (PSM), we assessed s[Na] elevations at 6 h post-treatment initiation and the rate of appropriate hyponatraemia correction between the RB-PC and PC groups. We defined the appropriate correction as a change in s[Na] in the range of 4-10 mEq/L within the first 24 h and ≤18 mEq/L within the first 48 h following corrective treatment initiation. Among 276 patients with profound hyponatraemia (s[Na] ≤120 mEq/L), 49 and 108 underwent treatment with RB-PC therapy and with PC therapy without RB, respectively. Post-PSM, 84 patients were selected and allocated to the RB-PC (n = 42) or PC group (n = 42). In PSM analysis, patients with RB-PC experienced a higher elevation in s[Na] at 6 h after treatment initiation than PC (4.0 vs 2.4 mEq/L, P < 0.001). The rate of appropriate correction was similar between the RB-PC and PC groups (90.5% vs 90.5%, P = 1). RB-PC can quickly elevate s[Na] levels and achieve appropriate correction of s[Na] in patients with profound hyponatraemia.
