Discovery of DS-1093a: An oral hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of renal anemia.

Inhibition of the hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) represents a promising strategy for discovering next-generation treatments for renal anemia. We discovered DS44470011 in our previous study, which showed potent in vitro activity and in vivo efficacy based on HIF-PHD inhibition. However, DS44470011 was also found to exert genotoxic effects. By converting the biphenyl structure, which is suspected to be the cause of this genotoxicity, to a 1-phenylpiperidine structure, we were able to avoid genotoxicity and further improve the in vitro activity and in vivo efficacy. Furthermore, through the optimization of pyrimidine derivatives, we discovered DS-1093a, which has a wide safety margin with potent in vitro activity and an optimal pharmacokinetic profile. DS-1093a achieved an increase in hemoglobin levels in an adenine-induced rat model of chronic kidney disease after its continuous administration for 4 days.

Predicting recurrence in intermediate­ and high­risk stage IB­IIB cervical cancer treated with adjuvant cisplatin and paclitaxel chemotherapy post­radical hysterectomy: The role of TBX2 expression.

Cervical cancer remains a significant global health concern despite advances in prevention and treatment. Current management for intermediate- to high-risk stage IB-IIB cervical cancer post-radical hysterectomy involves irradiation or concurrent chemoradiation, although patients can exhibit several adverse events. Adjuvant chemotherapy has emerged as a promising alternative; however, its efficacy remains unclear. T-box (TBX)2 is a transcription factor that is involved in the regulation of cell cycle progression during cancer and embryonic development. Additionally, elevated expression of TBX2 is associated with resistance to DNA-damaging chemotherapeutic agents, such as cisplatin, carboplatin and doxorubicin. The aim of the present study was to investigate the relationship between TBX2 expression and recurrence in patients receiving adjuvant cisplatin and paclitaxel (TP) chemotherapy post-radical hysterectomy. Additionally, the impact of TBX2 knockdown on cisplatin sensitivity was assessed in vitro. A retrospective analysis was performed on 100 patients. Patients were categorized into two groups based on recurrence within 2 years of treatment initiation: The non-recurrent group (n=85) and the recurrent group (n=15). TBX2 expression was assessed immunohistochemically, and multiple logistic regression analysis was performed to identify predictors of recurrence. Additionally, the impact of small interfering RNA-mediated TBX2 knockdown on cervical cancer cell sensitivity to cisplatin was evaluated. TBX2 expression was significantly higher in the recurrent group compared with that in the non-recurrent group (P<0.01). Patients were stratified into low TBX2 expression (weighted score ≤8; n=80) and high TBX2 expression (weighted score ≥9; n=20) groups. The high TBX2 expression group exhibited a higher recurrence rate compared with the low expression group (P<0.01). Multivariate analysis identified TBX2 expression as an independent predictor of recurrence (P<0.01). Moreover, TBX2 knockdown significantly enhanced cervical cancer cell sensitivity to cisplatin in vitro (P<0.05). These findings highlight TBX2 expression as a potential predictive biomarker for recurrence amongst patients with intermediate- to high-risk stage IB-IIB cervical cancer receiving adjuvant TP chemotherapy post-radical hysterectomy.

Corded and Hyalinized Endometrioid Endometrial Carcinoma: A Rare Case Treated With Robot-Assisted Surgery.

Endometrial carcinoma is the sixth most common cancer among women worldwide. Minimally invasive surgery (MIS) has become the preferred treatment, offering similar survival outcomes to laparotomy with lower complication rates. Corded and hyalinized endometrioid carcinoma (CHEC) is a rare and diagnostically challenging variant of endometrioid carcinoma, first described in 2005, characterized by a biphasic appearance of traditional low-grade endometrioid adenocarcinoma and corded and spindled cells embedded in a hyaline stroma. A 55-year-old nulligravid woman presented with abnormal genital bleeding for 10 days. Initial evaluations, including transvaginal ultrasonography and histological examination, confirmed adenocarcinoma. Imaging studies (magnetic resonance imaging [MRI] and computed tomography [CT]) revealed a thickened endometrium (11 mm) with no myometrial invasion, enlarged pelvic lymph nodes, or distant metastasis. Tumor markers were within normal ranges. She underwent robot-assisted laparoscopic total hysterectomy, bilateral adnexectomy, and pelvic lymph node biopsy using the da Vinci Xi system (Intuitive Surgical, Sunnyvale, CA). Histopathological examination revealed CHEC, with characteristic epithelioid and spindled cells arranged in cords within a hyalinized stroma. Immunohistochemical staining showed focal positivity for cytokeratin AE1/AE3, weak estrogen receptor positivity, and nuclear ß-catenin expression, distinguishing it from carcinosarcoma. The diagnosis was confirmed as CHEC, FIGO 2008 stage IA (pT1aN0M0). The patient remained disease-free 18 months post-surgery. CHEC is a rare variant of endometrioid carcinoma with unique histological features. It typically presents in younger patients at an early stage and has a favorable prognosis. Accurate diagnosis is crucial to differentiate it from more aggressive tumors like carcinosarcoma, preventing overtreatment. The immunohistochemical profile, particularly nuclear ß-catenin accumulation, is useful in distinguishing CHEC from carcinosarcoma. This is the first documented case of CHEC successfully treated with robot-assisted surgery. Increased awareness among pathologists and clinicians is essential for accurate diagnosis and optimal management of this rare tumor variant.

Discovery of DS44470011: An oral hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of renal anemia.

Inhibition of the hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) represents a promising strategy for discovering next-generation treatments for renal anemia. We identified a pyrimidine core with HIF-PHD inhibitory activity based on scaffold hopping of FG-2216 using crystal structures of HIF-PHD2 in complex with compound. By optimizing the substituents at the 2- and 6- positions of the pyrimidine core, we discovered DS44470011, which improves the effectiveness of erythropoietin (EPO) release in cells. Oral administration of DS44470011 to cynomolgus monkeys increased plasma EPO levels.

Comparison of characteristics of muscle magnetic resonance imaging findings in patients with antineutrophilic cytoplasmic antibody-associated vasculitis and polyarteritis nodosa.

AIM: This study aimed to analyze the muscle magnetic resonance imaging (MRI) findings of patients with antineutrophilic cytoplasmic antibody-associated vasculitis (AAV) and polyarteritis nodosa (PAN) presenting with clinical symptoms in the extremities. METHODS: Retrospective analysis was conducted on short tau inversion recovery MRI findings, with a focus on intramuscular vessels displaying abnormal perivascular signals, in 22 and eight patients with AAV and PAN, respectively. The number per unit area (4 cm2) and diameter of abnormal vessels on muscle MRI were compared between patients with AAV and those with PAN. Cut-off values, clinical sensitivity, and specificity for these indices were calculated from the receiver operating characteristic curves to distinguish between AAV and PAN, and the relationship between the indices and clinical findings in AAV was analyzed. RESULTS: The number of abnormal vessels per unit area was significantly higher in AAV compared to PAN (p < .05). Additionally, the diameter of the abnormal vessels was significantly higher in PAN than in AAV (p < .05). The presence of >6.44 abnormal vessels per unit area or ≤3.61 mm diameter of abnormal vessels was able to predict AAV (sensitivity, 0.955; specificity, 0.625). AAV patients with peripheral neuropathy exhibited a significantly higher number of abnormal vessels per unit area than those without peripheral neuropathy (p < .05). CONCLUSIONS: Muscle MRI can detect small- to medium-vessel vasculitis and be a valuable tool for distinguishing between patients with AAV and PAN experiencing clinical symptoms in the extremities.

Comparison of Bone Evaluation and Metal Artifact between Photon-Counting CT and Five Energy-Integrating-Detector CT under Standardized Conditions Using Cadaveric Forearms.

BACKGROUND: To compare the potential of various bone evaluations by considering photon-counting CT (PCCT) and multiple energy-integrating-detector CT (EIDCT), including three dual-energy CT (DECT) scanners with standardized various parameters in both standard resolution (STD) and ultra-high-resolution (UHR) modes. METHODS: Four cadaveric forearms were scanned using PCCT and five EIDCTs, by applying STD and UHR modes. Visibility of bone architecture, image quality, and a non-displaced fracture were subjectively scored against a reference EIDCT image by using a five-point scale. Image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were also compared. To assess metal artifacts, a forearm with radial plate fixation was scanned by with and without Tin filter (Sn+ and Sn-), and virtual monoenergetic image (VMI) at 120 keV was created. Regarding Sn+ and VMI, images were only obtained from the technically available scanners. Subjective scores and the areas of streak artifacts were compared. RESULTS: PCCT demonstrated significantly lower noise (p < 0.001) and higher bone SNR and CNR (p < 0.001) than all EIDCTs in both resolution modes. However, there was no significant difference between PCCT and EIDCTs in almost all subjective scores, regardless of scan modes, except for image quality where a significant difference was observed, compared to several EIDCTs. Metal artifact analysis revealed PCCT had larger artifact in Sn- and Sn+ (p < 0.001), but fewer in VMIs than three DECTs (p < 0.001 or 0.001). CONCLUSIONS: Under standardized conditions, while PCCT had almost no subjective superiority in visualizing bone structures and fracture line when compared to EIDCTs, it outperformed in quantitative analysis related to image quality, especially in lower noise and higher tissue contrast. When using PCCT to assess cases with metal implants, it may be recommended to use VMIs to minimize the possible tendency for artifact to be pronounced.

Metastasis of cervical cancer indicated by elevation of serum CA125 produced by mediastinal lymph nodes: a case report.

BACKGROUND: In patient assessment for recurrence of neoplasia, a biomarker that shows an elevated serum value before the first treatment is a candidate for follow-up examination. The biomarker squamous cell carcinoma antigen is usually utilized for follow-up of squamous cell cancer of the cervix. CASE PRESENTATION: We herein report a 30-year-old Japanese woman of postoperative metastasis of cervical squamous cell cancer to the mediastinal and supraclavicular lymph nodes as indicated by an elevated serum cancer antigen 125 concentration and not by the squamous cell carcinoma antigen value. After chemoradiotherapy and chemotherapy, the serum cancer antigen 125 concentration decreased to a normal value. Squamous cell carcinoma antigen was found to be distributed in both the squamous cell cancer tissue of the cervix and the supraclavicular lymph node metastatic tissue. By contrast, cancer antigen 125 was distributed in the supraclavicular lymph node metastatic tissue but not in the original squamous cell cancer tissue of the cervix. CONCLUSION: In this case, metastasis of cervical cancer to the mediastinal and supraclavicular lymph nodes was shown by the biomarker cancer antigen 125, which was not present in the original neoplasia.

Quantitative biomarkers for distinguishing bone metastasis and benign bone marrow lesions using turbo spin echo T1- and T2-weighted Dixon imaging at 3.0 T.

Objective: To assess the diagnostic performance and calculate the optimal threshold for quantitative biomarkers to differentiate bone metastasis and benign bone marrow lesions using turbo spin echo (TSE) Dixon images with a 3.0 T scanner. Materials and methods: Each 100 patients diagnosed with bone metastases and variable benign bone marrow lesions on spine MRI were included retrospectively. Images included in-phase (IP), opposed-phase (OP), water images (WI), and fat images (FI) by the TSE Dixon technique with T1WI and T2WI using a 3.0 T scanner. Regions of interest (ROI) of the lesions were manually drawn by two musculoskeletal radiologists independently, and the average signal intensity was recorded. The signal reduction rate from IP to OP (%drop) and a fat fraction (%fat) were calculated. Results: All biomarkers showed a significant difference between metastatic and benign lesions (P < 0.001). When comparing the AUCs, the %drop of T1WI had the highest AUC (0.934). Although the AUC of %fat from T2WI was significantly lower than that of other biomarkers, the %drop of T2WI was not significantly different from the %drop of T1WI (p = 0.339). The optimal threshold of %drop to differentiate metastatic and benign lesions was 22.0 in T1WI and 15.9 in T2WI. The inter-reader agreement was excellent for all biomarkers (0.82-0.86). Conclusion: While %drop of T1WI showed the highest diagnostic performance to differentiate bone metastasis from benign lesions, the %drop of T2WI showed a comparable ability using a threshold 15.9.

Intestinal­type mucinous carcinoma of the endometrium showing a polypoidal exophytic form: A case report.

Although endometrial cancer is a common malignancy in women, rare histological subtypes can pose diagnostic challenges. Primary endometrial intestinal-type mucinous carcinoma is a newly recognized subtype of endometrial cancer that differs from Müllerian-type endometrial mucinous carcinoma. The present case report documents a rare case of intestinal-type mucinous carcinoma of the endometrium showing a polypoidal exophytic form. The patient, an 80-year-old female, was incidentally diagnosed with a uterine tumor during a follow-up for vulvar Paget's disease. Clinical and imaging examinations revealed a localized mass within the uterine cavity. Hysteroscopy and subsequent histological examination confirmed the presence of intestinal-type mucinous carcinoma of the endometrium. Microscopically, the tumor displayed adenocarcinoma containing an intestinal-type glandular epithelium with mild nuclear atypia. It stained positive for the gastrointestinal markers mucin 2 and caudal type homeobox 2, and stained negatively for estrogen receptor α. The patient underwent surgery and adjuvant chemotherapy, with no evidence of recurrence at the latest follow-up 6 months after surgery. Endometrial intestinal-type mucinous carcinoma is a rare histological subtype of endometrial cancer. Differential diagnoses include Müllerian-type endometrial mucinous carcinoma, endocervical adenocarcinoma, metastasis from gastrointestinal tract adenocarcinoma and non-neoplastic gastric/intestinal metaplasia. However, the prognosis of endometrial intestinal-type mucinous carcinoma remains unclear due to limited reported cases. Existing evidence suggests a poorer prognosis compared with classical mucinous carcinomas of the endometrium. The present case, which is characterized by a polypoidal exophytic tumor without myometrial invasion, showed a favorable outcome. Further documentation and characterization of the aforementioned rare malignancy are necessary to enhance the understanding of its clinical physiology and outcomes. The present case report highlights the diagnostic challenges associated with intestinal-type mucinous endometrial carcinoma. The inclusion of this type of malignancy in the latest World Health Organization classification emphasizes the need for further comprehensive studies and case reports to expand the current knowledge on this rare histological subtype.

Intramuscular lesions in musculoskeletal MRI as a favourable prognostic sign in patients with anti-MDA5 antibody-positive dermatomyositis.

OBJECTIVES: Anti-differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis, which has been described as clinically amyopathic dermatomyositis, complicates rapidly progressive interstitial lung disease (ILD). Owing to the absence of significant muscle symptoms, musculoskeletal MRI is often not performed. In this study, we aimed to devise a simple evaluation method using musculoskeletal MRI findings to elucidate the relationship between MRI findings and ILD prognosis and development. METHODS: The medical records and MRI scans of the proximal muscles at the time of diagnosis were retrospectively reviewed for 28 patients with anti-MDA5 antibody-positive dermatomyositis who were admitted to The Jikei University Hospital and The Jikei University Kashiwa Hospital between January 2008 and March 2022. Three observers evaluated nine proximal muscles for high signals on either short-tau inversion recovery images and/or fat-saturated gadolinium-enhanced T1-weighted images in the fascia and/or in the margins of the muscles in contact with the fascia (fascial pattern), and/or high signals in the muscles away from the fascia (intramuscular pattern), and a consensus was reached. RESULTS: Of the 28 patients, 15 presented with 'radiological myositis', where an intramuscular pattern was observed at any site. Patients with radiological myositis had significantly higher survival rates than those without radiological myositis, despite the lower rate of triple therapy with prednisolone, calcineurin inhibitors and cyclophosphamide. The spread of ILD on chest CT negatively and significantly correlated with the proportion of intramuscular lesions. CONCLUSION: The detection of intramuscular lesions on musculoskeletal MRI using our novel evaluation method could be clinically useful as a favourable prognostic marker.

CLPTM1L expression predicts recurrence of patients with intermediate­ and high­risk stage IB­IIB cervical cancer undergoing radical hysterectomy followed by TP as adjuvant chemotherapy.

According to the National Comprehensive Cancer Network clinical practice guidelines of cervical cancer, concurrent chemoradiotherapy or radiotherapy is suggested for patients who receive radical hysterectomy and have intermediate- and high-risk cervical cancer. However, adjuvant chemotherapy has been increasingly chosen given the adverse events associated with chemoradiotherapy or radiotherapy and the increase in evidence regarding the efficacy of adjuvant chemotherapy. Given that adjuvant chemotherapy is not a standard treatment at present, if recurrence after adjuvant chemotherapy could be predicted, it would assist the decision of gynecological oncologists selecting which adjuvant therapy (chemotherapy or radiation therapy) to use. Cleft lip and palate transmembrane protein 1-like protein (CLPTM1L; also known as cisplatin resistance-related protein 9) is associated with apoptotic mechanisms and is related to the proliferation of the tumor cells and resistance against chemotherapy. In the present study, the association between CLPTM1L expression and recurrence of intermediate- and high-risk stage IB-IIB cervical cancer in patients undergoing radical hysterectomy followed by treatment with cisplatin and paclitaxel (TP) as adjuvant chemotherapy was determined. Patients were divided into two groups: Recurrence group and no-recurrence group. CLPTM1L expression was examined using immunohistochemistry in paraffin-embedded sections using weighted scores. Regarding the characteristics of the patients, a histology of non-squamous cell carcinoma, lymph node metastasis and parametrium invasion were more common in the recurrence group compared with the non-recurrence group. In the recurrence group, CLPTM1L expression was significantly higher than that in the no-recurrence group. Next, patients were divided into low and high-expression groups based on the weighted score with a cut-off value of 6. In the high expression group, patients exhibited a higher rate of recurrence (37.5 vs. 5.1%) and had worse overall survival. Multivariate analysis revealed that high CLPTM1L expression was independently related to recurrence. In in vitro analysis, small interfering RNA-mediated knockdown of CLPTM1L enhanced the sensitivity of cervical cancer cells to cisplatin. In conclusion, the present study revealed that CLPTM1L expression may be a predictive biomarker of recurrence of intermediate- and high-risk stage IB-IIB cervical cancer in patients undergoing radical hysterectomy followed by TP as adjuvant chemotherapy.

Real-world Efficacy and Safety of Bevacizumab for Advanced or Recurrent Müllerian Cancer: A Single-institutional Experience.

BACKGROUND/AIM: The efficacy and safety of bevacizumab for ovarian cancer have been reported in randomized phase III clinical trials. It is important to gather experience and data in a real-world setting. The objective of the present study was to evaluate the efficacy and safety of bevacizumab for patients with ovarian cancer in a real-world setting. PATIENTS AND METHODS: For front-line settings, patients with FIGO stage III-IV ovarian cancer treated using bevacizumab and chemotherapy after debulking surgery (Chemo + Bev group, n=79), in addition to those treated with only chemotherapy after debulking surgery (Chemo group; n=66), at our institute were reviewed retrospectively. For recurrent settings, patients with recurrent ovarian cancers treated with bevacizumab and any chemotherapy were reviewed retrospectively (n=65). RESULTS: In the front-line setting, the disease-free survival was significantly longer in the Chemo + Bev group compared with that in the Chemo group (p=0.021). Hypertension and proteinuria were found to be statistically more frequent in the Chemo + Bev group compared with that in the Chemo group (p=0.002 and p=0.004). In the recurrent setting, in platinum-sensitive patients, the response rate (RR) and the disease control ratio (DCR) were 78.4 and 94.1%, respectively. In platinum-resistant patients, the RR and the DCR were 28.6 and 57.1% respectively. The median progression-free survival was 18.3 and 7.1 months for platinum-sensitive recurrence and platinum-resistant recurrence, respectively. The major ≥ grade 3 adverse event was neutropenia. CONCLUSION: The present study provided encouraging real-world evidence of the efficacy and safety of bevacizumab for ovarian cancer in real-world.

Diagnostic Utility of Double-Echo Steady-State (DESS) MRI for Fracture and Bone Marrow Edema Detection in Adolescent Lumbar Spondylolysis.

To evaluate the ability of double-echo steady-state (DESS) MRI to detect pars interarticularis fracture and bone marrow edema (BME) in spondylolysis, 500 lumber pars interarticularis from 50 consecutive patients (38 males and 12 females, mean age 14.2 ± 3.28 years) with spondylolysis who underwent both MRI and CT within 1 week were evaluated. All participants were young athletes who complained of lower back pain. Fractures were classified into four grades and CT was used as a reference; BME was evaluated in a binary manner and STIR was used as a reference. The diagnostic performance of fractures on DESS and T1WI, and BME on DESS was assessed by two radiologists independently. For fracture detection, DESS showed high diagnostic performance at a sensitivity of 94%, specificity of 99.5%, and accuracy of 98.8%, whereas T1WI showed lower sensitivity (70.1%). Fracture grading performed by DESS showed excellent agreement with CT grading (Kappa = 0.9). For BME, the sensitivity, specificity, and accuracy of DESS were 96.5%, 100%, and 99.6%, respectively. The inter-rater agreement of DESS for fracture and BME was 0.8 and 0.85, respectively. However, the inter-rater agreement for fracture on T1WI was 0.52. DESS had high diagnostic performance for fracture and BME in pars interarticularis. In conclusion, DESS had potential to detect all critical imaging findings in spondylolysis and may replace the role of CT.

Carcinomatous meningitis from ovarian serous carcinoma: A case report.

Multifocal dissemination of cancer cells from the primary tumor sites to the subarachnoid, pia mater and cerebrospinal fluid (CSF) of the brain and spinal cord causes carcinomatous meningitis (CM). CM is rarely observed in patients with gynecological cancer. The present study described a 59-year-old woman who was diagnosed with CM as a recurrence of stage IIIC ovarian cancer, after presenting with headache and decreased level of consciousness. During adjuvant therapy following surgical debulking, she developed nausea and vomiting. The post-contrast fluid-attenuated inversion-recovery magnetic resonance imaging showed leptomeningeal enhancement on all sulci, particularly around the falx cerebri and cerebellar hemisphere. CM was suspected and CSF cytology revealed adenocarcinoma cells, thus confirming the diagnosis. Overall, although CM is rare, clinicians should be aware of this complication when patients with malignancies experience neurological symptoms, including headache, nausea and vomiting. Knowledge of this clinical entity should assist clinicians in ascertaining accurate diagnoses.

CT in osteoarthritis: its clinical role and recent advances.

Computed tomography (CT) is a widely available imaging method and considered as one of the most reliable techniques in bone assessment. Although CT has limited tissue contrast and needs radiation exposure, it has several advantages like fast scanning time and high spatial resolution. In this regard, CT has unique roles in osteoarthritis (OA) and its variable utilities have been reported. Hence, this review highlights the clinical role of CT in OA of representative joints. In addition, CT showed the several technical advancements recently, for example, acquiring the CT image with standing, obtaining the dual-energy data, and novel photon-counting detector development. Therefore, the recent studies and potential utility of these new CT systems in OA are also discussed.

Percutaneous transhepatic obliteration of a large portosystemic shunt associated with hepatic encephalopathy using a technique of n-butyl-2-cyanoacrylate injection inside hydrogel-coated coils: A case report.

Portosystemic shunts with cirrhosis may lead to hepatic encephalopathy (HE), which is often pharmacotherapy-resistant. We report a case of a 66-year-old female patient diagnosed with alcoholic cirrhosis and uncontrolled HE. She underwent percutaneous transhepatic obliteration (PTO) for treatment of a large portosystemic shunt from the left and right gastric veins to the azygos vein. We embolized the target veins using hydro-coated coils and filled them with n-butyl-2-cyanoacrylate (NBCA), leading to firmed obstruction of the large portosystemic shunt without NBCA migration, thus reducing the number of coils required. The HE symptoms improved after PTO and could thereafter be controlled with conservative therapy. Our results showed that PTO using an NBCA injection inside hydrogel-coated coils for a large portosystemic shunt associated with HE is effective and safe.

Microwave-Assisted Synthesis of the Red-Shifted Pentamethine Tetrahydroxanthylium Core with Absorbance within the Near Infrared-II Window.

Thirteen red-shifted pentamethine dimethyl and diethylamino tetrahydroxanthylium derivatives have been successfully synthesized via the microwave-assisted approach. The optimized conditions developed in the synthesis provided an excellent yield in expedited reaction time. These newly synthesized dyes show well-defined optical properties resulting from the diverse substitutions at the central meso positions. The majority of the compounds have a maximum wavelength of absorbance within 946-1022 nm with extinction coefficients in the range of 9700-110,680 M-1 cm-1 in various solvents such as MeOH, EtOH, DMSO, DCM, MeCN, and DMF. These fluorophores, to the best of our knowledge, are the first NIR-II small molecules synthesized using microwave chemistry. We also investigated these dyes for their NIR fluorescence imaging capabilities. Diethylamino-substituted compounds and bromination resulted in higher uptake in the adrenal gland compared to dimethylamino fluorophores. In addition, micellar structures of compounds 7 and 15 improved the targetability of the original dyes to the bone marrow, lymph nodes, and nerves. Overall, NIR-II imaging has the potential to visualize biologically targeted tissues in living organisms.

Inferior vena cava diameter on CT angiography predicts mesenteric angiography positive for extravasation in colonic diverticular bleeding.

PURPOSE: Transcatheter arterial embolization (TAE) for colonic diverticular bleeding (CDB), an established procedure for hemostasis, is sometimes complicated by spontaneous hemostasis and unclear bleeding site on angiography despite active arterial bleeding on preoperative computed tomography angiography (CTA). Therefore, to investigate and increase the feasibility of TAE, this retrospective study evaluates the clinical and radiological features related to positive extravasation on angiography. MATERIAL AND METHODS: Sixty CDB patients with extravasation on CTA underwent TAE between January 2011 and February 2021 and were divided into extravasation-positive (P-group; n = 25) and -negative groups (N-group; n = 35) based on the superior or inferior mesenteric angiography. Patient characteristics, laboratory findings, the diameter of the inferior vena cava (IVCD), the diameter of superior and inferior mesenteric veins, and technical outcomes were evaluated. RESULTS: TAE was successful in 24 patients in the P-group (96%) and 14 in the N-group (40%) (p < 0.001). Univariate analysis revealed "usage of anticoagulant" (p < 0.05) and "larger IVCD (p < 0.05) on preoperative CTA" to be significant predictors of positive extravasation. In the multivariate analysis, IVCD remained significant with an adjusted odds ratio of 1.17. The IVCD cutoff value was 13.6 mm (area under the curve = 0.72, sensitivity = 84.0%, specificity = 54.3%). There were no significant differences in other parameters. CONCLUSION: Measurement of IVCD in CDB with the cutoff value of 13.6 mm can be a simple and useful indicator to predict the detectability of extravasation following TAE procedures.

Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) followed by surgery is the current standard of treatment for locally advanced uterine cervical cancer; however, its value and outcomes remain contested. Identifying biomarkers that allow for the prediction of the effect of NAC efficacy before initiation of treatment is essential, in order to assist in choosing the optimum therapeutic regimen to maximize the beneficial outcomes of treatment. In the present retrospective study, 44 patients with locally advanced uterine cervical squamous cell carcinoma who underwent NAC were divided into two groups: A NAC successful group and a NAC failure group, depending on the efficacy of NAC. Subsequently, the association between Fyn expression, a non-receptor tyrosine kinase that is a member of the Src family kinases, and NAC efficacy was determined; Fyn expression was detected by immunohistochemistry and assessed using a weighted scoring method. Additionally, the effect of Fyn knockdown on the sensitivity of a uterine cervical cancer cell line to cisplatin was determined. Notably, there were no significant differences between the two groups of patients regarding their characteristics. Regarding overall survival, the NAC successful group had a significantly longer survival time than the NAC failure group (P=0.01). Furthermore, the expression levels of Fyn in tumor tissues were significantly lower in the NAC successful group compared with those in the NAC failure group (P=0.003). The patients were subsequently divided into two groups (high expression group and low expression group) according to a cutoff value of 3, which was determined by producing a receiver operating characteristic curve from the weighted scores. The low expression group was significantly more sensitive to NAC than the high expression group (P<0.001). In vitro experiments revealed that Fyn knockdown significantly enhanced the sensitivity of uterine cancer cells to cisplatin (P<0.05). In conclusion, Fyn expression may be a potentially useful biomarker for predicting the response to NAC in patients with locally advanced uterine cervical squamous cell carcinoma, and may also be a promising molecular target for the management of uterine cancer.