Conventional aryl hydrocarbon receptor (AhR) antagonists, which play a critical role in modulating tumor immune evasion, have shown limited clinical translation due to poor solubility, restricted systemic exposure, and dose-limiting toxicities. To overcome these limitations, we developed SB5794, a phosphate prodrug of the potent AhR antagonist SB2617, designed to improve aqueous solubility and pharmacokinetic properties. SB5794 exhibited markedly enhanced solubility and achieved more than six-fold higher systemic exposure in mice compared with SB2617, while fully retaining its in vitro AhR antagonistic activity. In syngeneic tumor models, SB5794 significantly inhibited tumor growth, and its combination with anti–PD-1 therapy further enhanced antitumor efficacy. However, repeated-dose studies revealed dose-dependent histopathological changes in the gastrointestinal tract, liver, and immune organs. Collectively, these findings demonstrate that SB5794 possesses improved drug-like properties and strong immunomodulatory activity, supporting its potential as a next-generation AhR-targeted immunotherapeutic candidate.

Purpose: While the benefit of neoadjuvant chemotherapy (NAC) has been established in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers, its effectiveness in achieving pathological complete response (pCR) and optimal patient selection in estrogen receptor (ER)-positive, HER2-negative breast cancers remain less clearly defined. This study aimed to identify immunohistochemistry (IHC)-based predictors of pCR and to develop a scoring model for ER-strong positive/HER2-negative breast cancer. Methods: Data from a prospective cohort were retrospectively analyzed. We included 522 patients with ER-strong positive/HER2-negative tumors who received NAC and surgery between 2008 and 2021. IHC markers including progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), and p53 were evaluated to identify predictors of pCR. Independent predictors of pCR from multivariate logistic regression were used to develop a weighted 4-point model. Model performance was assessed using receiver operating characteristic analysis. The prognostic impact of pCR was evaluated using KaplanMeier and Cox regression analyses. Results: Independent predictors of pCR included PR-negative status, positivity for basallike markers (EGFR or CK5/6), and Ki-67 ≥ 50%. The scoring model demonstrated good discrimination for pCR (area under the curve = 0.754). pCR rates increased stepwise, with scores of 4.9% (low), 10.7% (intermediate), and 36.2% (high). In the high-score group, pCR was significantly associated with improved disease-free survival (hazard ratio [HR], 0.09; p = 0.023) and distant metastasis-free survival (HR, 0.11; p = 0.035), whereas no significant survival differences according to pCR status were observed in the low and intermediate score groups. Conclusion This IHC-based model predicts pCR and helps identify subgroups in which pCR is associated with meaningful survival benefit following NAC in ER-positive/HER2-negative breast cancers. High-scoring patients may benefit from NAC, while patients with low- or intermediatescores may be better managed with surgery and endocrine therapy. This model may support personalized treatment decisions regarding NAC.

Purpose: Lobular carcinoma In Situ (LCIS) is a noninvasive lesion associated with an increased risk of invasive cancer. Since its removal from the tumor, node, metastasis classification in the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines, the clinical management of LCIS has shifted from surgery to surveillance. However, studies focusing on the risk and associated factors for invasive cancer development in pure LCIS without ductal carcinoma In Situ (DCIS) or invasive cancer remain limited. Methods: We retrospectively analyzed 106 patients diagnosed with pure LCIS between 2008 and 2018. This study evaluated the effect of tamoxifen use and histologic type on the development of invasive cancer. Results: All 106 patients underwent surgery, and nine (8.5%) developed invasive cancer over a median follow-up of 67.5 months. The incidence of invasive cancer was lower in the tamoxifen group (6.3%, n = 4) than in the non-tamoxifen group (11.9%, n = 5), although this difference was not statistically significant (p = 0.266). Pleomorphic LCIS had a significantly higher incidence of invasive cancer (30.0%, n = 3) than classic LCIS (6.3%, n = 6) (p = 0.045).Multivariable Cox regression analysis showed no significant difference in the risk of invasive cancer according to tamoxifen use (hazard ratio [HR], 2.031; 95% confidence interval [CI], 0.544–7.579; p = 0.292). However, pleomorphic LCIS showed a trend toward an increased risk of invasive cancer compared to classic LCIS (HR, 3.856; 95% CI, 0.922–16.126; p = 0.064). Conclusion Postoperative tamoxifen did not significantly lower invasive cancer development in patients with pure LCIS. Pleomorphic LCIS may carry a higher risk than classic LCIS. These findings require tailored follow-up and treatment strategies based on the histologic subtype of LCIS.

This study analyzed 80 biopsy specimens from pet hamsters in South Korea, focusing on naturally occurring tumors, particularly integumentary tumors. Tumors were most commonly found in the integumentary system (71.3%), followed by the reproductive (16.3%) and hematopoietic systems. In Djungarian hamsters, cutaneous atypical fibroma (27.8%) was the most frequent integumentary tumor, with the abdomen being the most affected site (42.6%). These findings highlight the importance of monitoring common neoplastic sites for better clinical management and preventative care, ultimately improving the health and longevity of pet hamsters.

A 25-year-old woman was referred for discomfort when breathing through her left nose. The patient had undergone augmentation rhinoplasty 5 years ago, after which hypertrophic scarring occurred in the left nostril. Several corticosteroid injections were administered as the first line of treatment, but with no symptom improvement. Therefore, we proceeded with surgical scar removal, with the use of a nasal conformer. However, scarring in the left nostril recurred. Accordingly, we proceeded with further surgical treatment using the scar folding technique. After scar folding, neither scarring nor nostril stenosis recurred during 1 year of postoperative follow-up. To summarize, herein, we report a case of hypertrophic scarring in the nostril that was successfully treated with the scar folding technique.

Multicentric cancer of the pectoral and ectopic breasts is extremely rare, and diagnosing this malignancy remains challenging because axillary breast cancer is easily misdiagnosed as lymph node metastasis. Moreover, there are no established treatment guidelines for this disease. We present our experience with a multicentric breast cancer patient who showed different responses to neoadjuvant chemotherapy (NAC) and underwent surgical treatments that differed from those in previous studies. In our case, the preoperative imaging of both lesions and subsequent core needle biopsy of each lesion were crucial, as these procedures confirm the diagnosis and help decide the chemotherapy regimen based on the subtype.After NAC, the patient underwent right breast-conserving surgery, sentinel lymph node biopsy (SLNB), and excision of accessory breast tissue in the right axilla. SLNB should be the initial step in staging multicentric breast cancer, unless imaging scan shows evidence of lymph node metastasis.

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare X-linked genetic condition caused by a gain-of-function mutation of arginine vasopressin receptor 2 gene, AVPR2. We report the case of a male neonate diagnosed with NSIAD based on his DNA sequence of the AVPR2 gene and the clinical course. He demonstrated a complete correction of hyponatremia using oral urea. We suggest that (1) sequencing analysis of the AVPR2 gene ought to be done in newborns with prolonged euvolemic hyponatremia, hypo-osmolality, high urinary sodium and normal/low or undetectable AVP levels, and that (2) oral urea is a safe and effective treatment option in infants diagnosed with NSIAD until the patients are grown-up.

BACKGROUND AND PURPOSE: Discrepancies between objectively measured sleep and subjective sleep perception in patients with insomnia have been reported. However, few studies have investigated sleep-state misperception in patients with obstructive sleep apnea (OSA). We designed this study to 1) delineate the factors that could affect this discrepancy and 2) infer an underlying mechanism in patients with OSA. METHODS: We recruited patients who visited our sleep clinic for the evaluation of their snoring and/or observed OSA. Participants completed a structured questionnaire and underwent overnight polysomnography. On the following day, five sessions of the multiple sleep latency test (MSLT) were applied. We divided the patients into two groups: normal sleep perception and abnormal perception. The abnormal-perception group included patients whose perceived total sleep time was less than 80% of that measured in polysomnography. RESULTS: Fifty OSA patients were enrolled from a university hospital sleep clinic. Excessive daytime sleepiness, periodic limb movement index (PLMI), and the presence of dreaming were positively associated with poor sleep perception. REM sleep near the sleep termination exerted important effects. Respiratory disturbance parameters were not related to sleep perception. There was a prolongation in the sleep latency in the first session of the MSLT and we suspected that a delayed sleep phase occurred in poor-sleep perceivers. CONCLUSIONS: As an objectively good sleep does not match the subjective good-sleep perception in OSA, physicians should keep in mind that OSA patients who perceive that they have slept well does not mean that their OSA is less severe.
Dreams ; Extremities ; Humans ; Polysomnography* ; Sleep Apnea, Obstructive* ; Sleep Initiation and Maintenance Disorders ; Sleep, REM ; Snoring

No abstract available.
Bowen's Disease* ; Porokeratosis*