Augmented interpretation of HER2, ER, and PR in breast cancer by artificial intelligence analyzer: enhancing interobserver agreement through a reader study of 201 cases.

BACKGROUND: Accurate classification of breast cancer molecular subtypes is crucial in determining treatment strategies and predicting clinical outcomes. This classification largely depends on the assessment of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) status. However, variability in interpretation among pathologists pose challenges to the accuracy of this classification. This study evaluates the role of artificial intelligence (AI) in enhancing the consistency of these evaluations. METHODS: AI-powered HER2 and ER/PR analyzers, consisting of cell and tissue models, were developed using 1,259 HER2, 744 ER, and 466 PR-stained immunohistochemistry (IHC) whole-slide images of breast cancer. External validation cohort comprising HER2, ER, and PR IHCs of 201 breast cancer cases were analyzed with these AI-powered analyzers. Three board-certified pathologists independently assessed these cases without AI annotation. Then, cases with differing interpretations between pathologists and the AI analyzer were revisited with AI assistance, focusing on evaluating the influence of AI assistance on the concordance among pathologists during the revised evaluation compared to the initial assessment. RESULTS: Reevaluation was required in 61 (30.3%), 42 (20.9%), and 80 (39.8%) of HER2, in 15 (7.5%), 17 (8.5%), and 11 (5.5%) of ER, and in 26 (12.9%), 24 (11.9%), and 28 (13.9%) of PR evaluations by the pathologists, respectively. Compared to initial interpretations, the assistance of AI led to a notable increase in the agreement among three pathologists on the status of HER2 (from 49.3 to 74.1%, p < 0.001), ER (from 93.0 to 96.5%, p = 0.096), and PR (from 84.6 to 91.5%, p = 0.006). This improvement was especially evident in cases of HER2 2+ and 1+, where the concordance significantly increased from 46.2 to 68.4% and from 26.5 to 70.7%, respectively. Consequently, a refinement in the classification of breast cancer molecular subtypes (from 58.2 to 78.6%, p < 0.001) was achieved with AI assistance. CONCLUSIONS: This study underscores the significant role of AI analyzers in improving pathologists' concordance in the classification of breast cancer molecular subtypes.

Prevalence and Long-term Outcomes of CT Interstitial Lung Abnormalities in a Health Screening Cohort.

Background The association between interstitial lung abnormalities (ILAs) and long-term outcomes has not been reported in Asian health screening populations. Purpose To investigate ILA prevalence in an Asian health screening cohort and determine rates and risks for ILA progression, lung cancer development, and mortality within the 10-year follow-up. Materials and Methods This observational, retrospective multicenter study included patients aged 50 years or older who underwent chest CT at three health screening centers over a 4-year period (2007-2010). ILA status was classified as none, equivocal ILA, and ILA (nonfibrotic or fibrotic). Progression was evaluated from baseline to the last follow-up CT examination, when available. The log-rank test was performed to compare mortality rates over time between ILA statuses. Multivariable Cox proportional hazards models were used to assess factors associated with hazards of ILA progression, lung cancer development, and mortality. Results Of the 2765 included patients (mean age, 59 years ± 7 [SD]; 2068 men), 94 (3%) had a finding of ILA (35 nonfibrotic and 59 fibrotic ILA) and 119 (4%) had equivocal ILA. The median time for CT follow-up and the entire observation was 8 and 12 years, respectively. ILA progression was observed in 80% (48 of 60) of patients with ILA over 8 years. Those with fibrotic and nonfibrotic ILA had a higher mortality rate than those without ILA (P < .001 and P = .01, respectively) over 12 years. Fibrotic ILA was independently associated with ILA progression (hazard ratio [HR], 10.3; 95% CI: 6.4, 16.4; P < .001), lung cancer development (HR, 4.4; 95% CI: 2.1, 9.1; P < .001), disease-specific mortality (HR, 6.7; 95% CI: 3.7, 12.2; P < .001), and all-cause mortality (HR, 2.5; 95% CI: 1.6, 3.8; P < .001) compared with no ILA. Conclusion The prevalence of interstitial lung abnormalities (ILAs) in an Asian health screening cohort was approximately 3%, and fibrotic ILA was an independent risk factor for ILA progression, lung cancer development, and mortality. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Hatabu and Hata in this issue.

Intracellular pH-Regulating Nanoparticles to Improve Anticancer Drug Efficacy for Cancer Treatment.

Here, we describe an intracellular pH-regulating nanoparticle (IPRN), coencapsulated with chemosensitizers and anticancer agents for effective and safe cancer treatment. IPRN contains a tubulysin derivative (TUB), a hydrophobic anticancer drug, and pantoprazole (PTZ), a hydrophilic proton-pump inhibitor. IPRN with a size of 62 nm has an anionic surface charge and is stable for at least two weeks under storage conditions, though PTZ and TUB encapsulated in IPRN showed different drug release patterns. PTZ was released before TUB, controlling the cancer's intracellular pH, maintaining a pH at which TUB can work well. The encapsulated PTZ increased the pH of endolysosomes and inhibited ion trapping, with TUB ionization, thereby exhibiting increased cytotoxicity compared with free TUB observed in various cancer cell lines, such as human liver adenocarcinoma, human glioblastoma, and human pancreatic carcinoma. IPRN exhibited a 1.9-fold improved tumor growth inhibitory effect in a human liver adenocarcinoma-bearing mouse model, while minimizing the hepatotoxicity of free TUB. Thus, nanomedicines that contain both a chemosensitizer and an anticancer agent, such as IPRN, are expected to be next-generation anticancer agents that reduce the side effects of anticancer drugs and increase the therapeutic effect.

Effect of Rubus Occidentalis Extract on Metabolic Parameters in Subjects with Prediabetes: A Proof-of-concept, Randomized, Double-blind, Placebo-controlled Clinical Trial.

Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12-week, randomized, double-blind, placebo-controlled trial. Forty-four patients (age 59.0 ± 8.2 years, 70.5% females, HbA1c 5.8 ± 0.4%) were divided into placebo (n = 13), low-dose RO extract (LRE; n = 14), or high-dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75-g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (-28.1 ± 42.4 vs. +13.4 ± 52.6 mg/dL, p < 0.05). Homoeostasis model assessment-B was increased (+17.11 ± 10.69, +5.24 ± 4.10, and +0.86 ± 6.01 in HRE, LRE, and placebo, respectively, p < 0.05). Serum levels of monocyte chemoattractant protein-1 and oxidized low-density lipoprotein were significantly decreased by treatment in a dose-dependent manner (monocyte chemoattractant protein-1: -35.0 ± 21.2, +8.4 ± 18.1, and +24.2 ± 14.5; oxidized low-density lipoprotein: -19.7 ± 8.5, -13.1 ± 7.2, and -2.2 ± 11.0 in the HRE, LRE, and placebo, respectively, p < 0.05). The results support the beneficial effects of RO extract on the control of glycemia and vascular inflammation in prediabetic patients. (ClinicalTrials.gov: NCT01964703). Copyright © 2016 John Wiley & Sons, Ltd.

Risk factors of radiation dose in patients undergoing peripherally-inserted central catheter procedure using conventional angiography equipment and flat panel detector-based mobile C-arm fluoroscopy.

BACKGROUND: Although peripherally-inserted central catheter (PICC) insertion is commonly performed under fluoroscopic guidance, few reports have addressed performance and dosimetry when PICC is inserted under C-arm fluoroscopy. PURPOSE: To evaluate the risk factors of radiation dose in performing PICC insertion using flat panel detector-based mobile C-arm fluoroscopy and a conventional angiography machine. MATERIAL AND METHODS: Ninety-eight patients underwent the PICC procedure using conventional angiography equipment (n=49) or flat panel detector-based mobile C-arm fluoroscopy (n=49). Data were prospectively analyzed from July to November 2012. Dose-area product (DAP), tube voltage, tube current, fluoroscopy time, and image quality measured on a 5-point scale were estimated and compared using appropriate statistical tests. RESULTS: There were no significant differences in tube voltage, fluoroscopy time, and image quality between conventional angiography and mobile C-arm fluoroscopy. DAP, mean arm tube current, and tube current in chest fluoroscopy were significantly lower in mobile C-arm fluoroscopy than using the conventional angiography machine (P < 0.05). Multivariate analysis identified tube current in chest fluoroscopy, arm tube current, and fluoroscopy equipment as significant risk factors for elevated radiation dose in PICC insertion. CONCLUSION: PICC insertion can be performed using flat panel detector-based mobile C-arm fluoroscopy instead of a conventional angiography machine. Image quality and fluoroscopy time were not different between the two systems and the use of C-arm fluoroscopy significantly reduced radiation dose.

Effects of black raspberry on lipid profiles and vascular endothelial function in patients with metabolic syndrome.

Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (-22.8 ± 30.4 mg/dL vs. -1.9 ± 31.8 mg/dL, p < 0.05, respectively) and total cholesterol/HDL ratio (-0.31 ± 0.64 vs. 0.07 ± 0.58, p < 0.05, respectively) were significantly greater in the group with black raspberry than in the placebo group. Increases in baFMD at the 12-week follow-up were significantly greater in the group with black raspberry than in the placebo group (0.33 ± 0.44 mm vs. 0.10 ± 0.35 mm, p < 0.05, respectively). Decreases from the baseline in IL-6 (-0.4 ± 1.5 pg/mL vs. -0.1 ± 1.0 pg/mL, p < 0.05, respectively) and TNF-α (-2.9 ± 4.7 pg/mL vs. 0.1 ± 3.6 pg/mL, p < 0.05, respectively) were significantly greater in the group with black raspberry. The use of black raspberry significantly decreased serum total cholesterol level and inflammatory cytokines, thereby improving vascular endothelial function in patients with metabolic syndrome during the 12-week follow-up.

Caffeic Acid Enhances Anticancer Drug-induced Apoptosis in Acid-adapted HCT116 Colon Cancer Cells.

BACKGROUND/AIM: Apoptosis resistance in cancer cells adapted to acidic microenvironments poses a challenge for effective treatment. This study investigated the potential use of caffeic acid as an adjunct therapy to overcome drug resistance in colorectal cancer cells under acidic conditions. MATERIALS AND METHODS: Long-term exposure to low-pH conditions induced resistance in HCT116 colorectal cancer cells. The effects of caffeic acid on proliferation, clonogenicity, and apoptosis induction were assessed alone and in combination with oxaliplatin and 5-Fluorouracil. The signaling pathways involved in drug resistance were examined by assessing the activities of PI3K/Akt and ERK1/2. RESULTS: Caffeic acid inhibited the proliferation and clonogenicity of acid-adapted cancer cells, and enhanced apoptosis when combined with anticancer drugs. Mechanistically, caffeic acid attenuated the hyperactivation of the PI3K/Akt and ERK1/2 signaling pathways associated with drug resistance. CONCLUSION: Caffeic acid is a promising therapeutic agent for targeting resistant cancer cells in acidic microenvironments. Its ability to inhibit proliferation, sensitize cells to apoptosis, and modulate signaling pathways highlights its potential for overcoming drug resistance in cancer therapy.

Inflamed immune phenotype predicts favorable clinical outcomes of immune checkpoint inhibitor therapy across multiple cancer types.

BACKGROUND: The inflamed immune phenotype (IIP), defined by enrichment of tumor-infiltrating lymphocytes (TILs) within intratumoral areas, is a promising tumor-agnostic biomarker of response to immune checkpoint inhibitor (ICI) therapy. However, it is challenging to define the IIP in an objective and reproducible manner during manual histopathologic examination. Here, we investigate artificial intelligence (AI)-based immune phenotypes capable of predicting ICI clinical outcomes in multiple solid tumor types. METHODS: Lunit SCOPE IO is a deep learning model which determines the immune phenotype of the tumor microenvironment based on TIL analysis. We evaluated the correlation between the IIP and ICI treatment outcomes in terms of objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) in a cohort of 1,806 ICI-treated patients representing over 27 solid tumor types retrospectively collected from multiple institutions. RESULTS: We observed an overall IIP prevalence of 35.2% and significantly more favorable ORRs (26.3% vs 15.8%), PFS (median 5.3 vs 3.1 months, HR 0.68, 95% CI 0.61 to 0.76), and OS (median 25.3 vs 13.6 months, HR 0.66, 95% CI 0.57 to 0.75) after ICI therapy in IIP compared with non-IIP patients, respectively (p<0.001 for all comparisons). On subgroup analysis, the IIP was generally prognostic of favorable PFS across major patient subgroups, with the exception of the microsatellite unstable/mismatch repair deficient subgroup. CONCLUSION: The AI-based IIP may represent a practical, affordable, clinically actionable, and tumor-agnostic biomarker prognostic of ICI therapy response across diverse tumor types.

Development of a radial pulse tonometric (RPT) sensor with a temperature compensation mechanism.

Several RPT sensors have been developed to acquire objective and quantitative pulse waves. These sensors offer improved performance with respect to pressure calibration, size and sensor deployment, but not temperature. Since most pressure sensors are sensitive to temperature, various temperature compensation techniques have been developed, but these techniques are largely inapplicable to RPT sensors due to the size restrictions of the sensor, and incompatibility between the compensation techniques and the RPT sensor. Consequently, in this paper a new RPT sensor comprising six piezoresistive pressure sensors and one thermistor has been developed through finite element analysis and then a suitable temperature compensation technique has been proposed. This technique compensates for temperature variations by using the thermistor and simple compensation equations. As verification of the proposed compensation technique, pulse waves of all types were successfully compensated for temperature changes.

Nanocracker capable of simultaneously reversing both P-glycoprotein and tumor microenvironment.

Here, we describe a multidrug-resistant nanocracker (MDRC) that can treat multi-drug resistant (MDR) cancer by recognizing the acidic microenvironment and inhibiting two mechanisms of MDR such as P-glycoprotein (P-gp) and vacuolar-type ATPase (V-ATPase). MDRC is a liposome formulation co-loading pantoprazole (PZ) and paclitaxel (PTX). PZ acts as a chemosensitizer that enhances the MDR cancer treatment effect of PTX by disrupting the pH gradient and inhibiting P-gp. MDRC-encapsulated PZ and PTX have different release rates, with PZ released within 12 h and PTX sustained release for 48 h in the plasma. MDRC could increase cell uptake by inhibiting the P-gp overexpressed MCF-7/mdr cells and UV-2237M cells, which are human breast MDR cancer cells and murine fibrosarcoma cells, respectively. MDRC can also increase the cytotoxic efficacy of PTX by increasing intracellular pH. MDRC has a 10.5-fold reduced IC50 value in the P-gp overexpressed human breast adenocarcinoma and a 6.3- to 9.5-fold reduced IC50 value in the P-gp non-expressed human breast adenocarcinoma compared to the mixture of PZ and PTX, respectively. Intravenous injection of MDRC did not cause weight loss, liver dysfunction, or major organ toxicity. MDRC exhibited 80% complete remission of murine fibrosarcoma. The excellent therapeutic effect of MDRC on MDR tumors was accompanied by an increase in dendritic cell maturation and cytotoxic T cells. In other words, MDRC has the potential to terminate MDR therapy through the complete remission of MDR tumors.

Synergistic Approach of Antibody-Photosensitizer Conjugate Independent of KRAS-Mutation and Its Downstream Blockade Pathway in Colorectal Cancer.

Here, a novel approach is presented to improve the efficacy of antibody-drug conjugates (ADC) by integrating antibody-mediated immunotherapy and photodynamic therapy (PDT) in a combination therapy system utilizing an antibody-photosensitizer conjugate (APC) platform based on a poloxamer polymer linker. To specifically target Kirsten rat sarcoma 2 viral oncogene homolog (KRAS)-mutated cancer cells, an antibody antiepidermal growth factor receptor (EGFR), cetuximab, with a poloxamer linker coupled with the photosensitizer chlorin e6 through click chemistry (cetuximab-maleimide-poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)-chlorine e6 conjugate, CMPXC) is synthesized. CMPXC is cytotoxic upon laser treatment, achieving a 90% cell death by suppressing KRAS downstream signaling pathways associated with ERK and AKT proteins, confirmed using RNA sequencing analysis. In KRAS-mutated colorectal cancer mouse models, CMPXC significantly enhances antitumor efficacy compared with cetuximab treatment alone, resulting in an 86% reduction in tumor growth. Furthermore, CMPXC treatment leads to a 2.24- and 1.75-fold increase in dendritic and priming cytotoxic T cells, respectively, highlighting the immune-activating potential of this approach. The findings suggest that the APC platform addresses the challenges associated with ADC development and EGFR-targeted therapy, including the synergistic advantages of antibody-mediated immunotherapy and PDT.

Anticancer Effect of Gallic Acid on Acidity-Induced Invasion of MCF7 Breast Cancer Cells.

The acidic tumor environment has emerged as a crucial factor influencing the metastatic potential of cancer. We investigated the effect of an acidic environment on the acquisition of metastatic properties in MCF7 breast cancer cells and explored the inhibitory effects of gallic acid. Prolonged exposure to acidic culture conditions (over 12 weeks at pH 6.4) induced the acquisition of migratory and invasive properties in MCF7 cells, accompanied by increased expression of Matrix Metalloproteinase 2 and 9 (MMP2 and MMP9, respectively), together with alterations in E-cadherin, vimentin, and epithelial-to-mesenchymal transition markers. Gallic acid effectively inhibited the survival of acidity-adapted MCF7 (MCF7-6.4/12w) cells at high concentrations (>30 µM) and reduced metastatic characteristics induced by acidic conditions at low concentration ranges (5-20 µM). Moreover, gallic acid suppressed the PI3K/Akt pathway and the nuclear accumulation of ß-catenin, which were elevated in MCF7-6.4/12w cells. These findings highlight the potential of gallic acid as a promising therapeutic agent for metastatic traits in breast cancer cells under acidic conditions.

Gastrointestinal AA Amyloidosis following Recurrent SARS-CoV-2 Infection: A Case Report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with the overproduction of serum amyloid A protein, resulting in systemic AA amyloidosis. In this report, we describe a case of gastrointestinal (GI) AA amyloidosis following SARS-CoV-2 infection. A 75-year-old male presented to the emergency department with upper abdominal pain 6 weeks post kidney transplantation. He had a history of SARS-CoV-2 infection 4 weeks prior. On day 7 of hospitalization, while receiving conservative management, the patient developed symptoms of cough and fever, leading to a diagnosis of SARS-CoV-2 reinfection. The patient's abdominal pain persisted, and hematochezia developed on day 30 of hospitalization. Esophagogastroduodenoscopy and colonoscopy revealed multiple ulcers in the stomach and colon, with histologic findings revealing the presence of amyloid A. The patient was managed conservatively and was also given remdesivir for the SARS-CoV-2 infection. His clinical symptoms subsequently improved, and endoscopic findings demonstrated improvement in multiple gastric ulcers. GI amyloidosis may be a subacute complication following SARS-CoV-2 infection in immunocompromised patients.

Case Report: A case of ultra-late recurrence of KIF13A-RET fusion non-small cell lung cancer response to selpercatinib.

Background: Cancer recurrence remains a significant problem, and most postoperative recurrences of non-small cell lung cancer (NSCLC) develop within 5 years after resection. We present a rare case of ultra-late recurrence of NSCLC accompanying choroidal metastasis with KIF13A-RET fusion 14 years after the definitive surgery. Case description: A 48-year-old female patient who had never-smoked presented with decreased visual acuity. She had been treated with right upper lobe lobectomy followed by adjuvant chemotherapy 14 years prior. Fundus photographs revealed bilateral choroidal metastatic lesions. Positron emission tomography-computed tomography (PET-CT) scans showed extensive bone metastases and focal hypermetabolism in the left uterine cervix. An excision biopsy of the uterus showed primary lung adenocarcinoma with immunohistochemistry of TTF-1+. Plasma next-generation sequencing (NGS) identified the presence of KIF13A-RET fusion. After 6 months of selpercatinib therapy, PET-CT revealed a partial response for bone and uterine metastasis and stable disease for choroidal lesions. Conclusion: In this case report, we are reporting a rare case of ultra-late recurrence of NSCLC in a patient with choroidal metastasis. Furthermore, the diagnosis of NSCLC with RET fusion was based on liquid-based NGS rather than tissue-based biopsy. The patient showed a good response to selpercatinib, which supports the efficacy of selpercatinib as a treatment for RET-fusion-positive NSCLC with choroidal metastasis.

Deep learning model improves tumor-infiltrating lymphocyte evaluation and therapeutic response prediction in breast cancer.

Tumor-infiltrating lymphocytes (TILs) have been recognized as key players in the tumor microenvironment of breast cancer, but substantial interobserver variability among pathologists has impeded its utility as a biomarker. We developed a deep learning (DL)-based TIL analyzer to evaluate stromal TILs (sTILs) in breast cancer. Three pathologists evaluated 402 whole slide images of breast cancer and interpreted the sTIL scores. A standalone performance of the DL model was evaluated in the 210 cases (52.2%) exhibiting sTIL score differences of less than 10 percentage points, yielding a concordance correlation coefficient of 0.755 (95% confidence interval [CI], 0.693-0.805) in comparison to the pathologists' scores. For the 226 slides (56.2%) showing a 10 percentage points or greater variance between pathologists and the DL model, revisions were made. The number of discordant cases was reduced to 116 (28.9%) with the DL assistance (p < 0.001). The DL assistance also increased the concordance correlation coefficient of the sTIL score among every two pathologists. In triple-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients who underwent the neoadjuvant chemotherapy, the DL-assisted revision notably accentuated higher sTIL scores in responders (26.8 ± 19.6 vs. 19.0 ± 16.4, p = 0.003). Furthermore, the DL-assistant revision disclosed the correlation of sTIL-high tumors (sTIL ≥ 50) with the chemotherapeutic response (odd ratio 1.28 [95% confidence interval, 1.01-1.63], p = 0.039). Through enhancing inter-pathologist concordance in sTIL interpretation and predicting neoadjuvant chemotherapy response, here we report the utility of the DL-based tool as a reference for sTIL scoring in breast cancer assessment.

Histone H4 deacetylation down-regulates catalase gene expression in doxorubicin-resistant AML subline.

We explored if epigenetic mechanisms could be involved in the down-regulated expression of catalase gene (CAT) in the doxorubicin-resistant acute myelogenous leukemia (AML)-2/DX100 cells. Down-regulated CAT expression in AML-2/DX100 cells was completely recovered after treatment of hydrogen peroxide (H(2)O(2)) and histone deacetylase inhibitor, trichostatin A (TSA) but was increased slightly by the treatment of DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-AdC). Bisulfite-sequencing PCR revealed that a CpG island of CAT was not methylated in AML-2/DX100 cells. Chromatin immunoprecipitation assay confirmed that acetylation of histone H4 in AML-2/DX100 cells significantly decreased as compared with that in AML-2/WT cells, which was significantly increased by TSA more than 5-AdC. Meanwhile, overexpression of other up-regulated peroxidase genes appears to make compensation for decreased H(2)O(2)-scavenging activity for the down-regulated CAT expression in AML-2/DX100 cells. These results suggest that histone H4 deacetylation is responsible for the down-regulated CAT expression in AML-2/DX100 cells, which are well adapted to oxidative stress.

Clinicopathological Characteristics of Primary Pulmonary Hodgkin Lymphoma (PPHL): Two Institutional Experiences with Comprehensive Literature Review of 115 PPHL Cases.

Primary pulmonary Hodgkin lymphoma (PPHL) is an extremely rare condition. Its clinicopathological characteristics remain unclear because of the limited number of patients with PPHL. The aim of this study was to comprehensively analyze the clinicopathological characteristics of PPHL. We reviewed the electronic medical records and pathology slides of our 10 PPHL patients. The female-to-male ratio was 6:4, and the mean age was 41 years. Although three patients had no symptoms, seven had localized or generalized symptoms, including cough, sputum, chest discomfort/pain, and weight loss. Some cases had not been diagnosed as PPHL in the initial needle biopsy. Four patients underwent surgical resection. With chemotherapy, eight patients achieved complete remission. We also conducted a thorough literature review on 105 previously reported PPHL cases. Among a total of 115 PPHL cases, the most common subtype was nodular sclerosis (37.4%). More than half of the cases (55%) were clinically suspected as infectious pneumonia. Of 61 patients whose biopsies were available, 27 (44.3%) were diagnosed correctly as Hodgkin lymphoma, whereas the misdiagnoses included tuberculosis, Langerhans cell histiocytosis, solitary fibrous tumor, and adenocarcinoma. We demonstrated that PPHL represents a diagnostic challenge on small biopsies. Recognizing that this rare tumor can mimic infectious and inflammatory diseases as well as malignancies is important because the accurate diagnosis of PPHL is essential for adequate clinical management.

Molecular Basis of Resveratrol-Induced Resensitization of Acquired Drug-Resistant Cancer Cells.

Multidrug resistance (MDR) to anticancer drugs remains a serious obstacle to the success of cancer chemotherapy. Resveratrol, a polyphenol, present in natural products exerts anticancer activity and acts as a potential MDR inhibitor in various drug-resistant cancer cells. In the process of resensitization of drug-resistant cancer cells, resveratrol has been shown to interfere with ABC transporters and drug-metabolizing enzymes, increase DNA damage, inhibit cell cycle progression, and induce apoptosis and autophagy, as well as prevent the induction of epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs). This review summarizes the mechanisms by which resveratrol counteracts MDR in acquired drug-resistant cancer cell lines and provides a critical basis for understanding the regulation of MDR as well as the development of MDR-inhibiting drugs.

[Mediastinal Teratoma: A Pictorial Essay]. / ì¢ ê²©ë™ ê¸°í˜•ì¢ : 임상 화보.

The mediastinum is the most prevalent site of extragonadal teratomas. Patients with mediastinal mature teratomas are usually young adults, and the condition does not show significant sexual differences. Mediastinal teratomas are mostly located in the anterior mediastinum. Patients are usually asymptomatic, although they can have several complications when the teratomas become large or rupture. Most mediastinal teratomas can be diagnosed using CT. Diagnosing ruptured or malignant teratomas is challenging because of their atypical clinical and radiological presentations. In this article, we describe various manifestations of mediastinal teratomas, with an emphasis on radiologic features.

Lipid raft-dependent death receptor 5 (DR5) expression and activation are critical for ursodeoxycholic acid-induced apoptosis in gastric cancer cells.

Ursodeoxycholic acid (UDCA) is known as a suppressor of cholestatic liver diseases and colorectal cancer development. Here, we demonstrate that UDCA induces apoptosis without necrotic features in SNU601, SNU638, SNU1 and SNU216 human gastric cancer cells, implying its possible use as an effective chemotherapeutic agent in treatment of gastric cancer. UDCA-induced apoptosis was dominantly mediated by an extrinsic pathway dependent on caspase-8, -6 and -3. UDCA increased expression of death receptor 5 [(DR5), also known as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2], and this DR appeared to be responsible for UDCA-induced apoptosis, as evidenced by DR5 knockdown. UDCA triggered formation of lipid rafts that played crucial roles in UDCA-induced apoptotic actions. Lipid rafts were required not only for provision of a proper site for DR5 action but also for mediation of DR5 expression. In addition, reactive oxygen species (ROS) and protein kinase C (PKC) δ appeared to be implicated in UDCA-induced raft-dependent DR5 expression. Our results indicate that UDCA-induced apoptosis is mediated by DR5 expression, which is regulated by the raft formation/ROS production/PKCδ activation pathway and DR5 localization into lipid rafts in gastric cancer cells. Tumor-suppressive activity of UDCA was confirmed in an in vivo system: UDCA (120 mg/kg/day) significantly decreased tumor growth in gastric cancer xenograft mice. Taken together, our results demonstrate that UDCA can be used as a potent chemotherapeutic agent for treatment of gastric cancer.