Recent advances in cancer biology have revolutionized the development of targeted and combination therapies, offering new avenues for improving cancer management. Among the central molecular regulators, the mammalian target of rapamycin (mTOR) plays a pivotal role in orchestrating cell growth, metabolism, and survival. Aberrant activation of mTOR signaling driven by genetic mutations or dysregulation of upstream pathways such as phosphoinositide 3-kinase (PI3K)/AKT has been strongly implicated in cancer progression, metastasis, and therapeutic resistance. Consequently, mTOR has emerged as a promising target for anticancer drug development. Although synthetic mTOR inhibitors, including rapamycin and its analogs (rapalogs), have shown clinical benefits, their limited efficacy and the emergence of resistance have highlighted the need for novel strategies. Natural product-derived mTOR modulators have gained increasing attention due to their multi-targeted mechanisms of action, simultaneously modulating mTOR and its upstream or parallel signaling networks. These compounds exhibit potent anticancer properties, including suppression of tumor growth, induction of apoptosis, and reversal of drug resistance. This review elucidates the biological functions of mTOR in tumorigenesis and delineates its regulatory mechanisms underlying malignant phenotypes. Furthermore, it emphasizes the therapeutic promise of natural products as a rich source of mTOR inhibitors, providing insights for the rational design of innovative cancer therapies and combination regimens.

This study aimed to clarify the lymphatic network around the anorectum using cadavers and consider a treatment strategy for locally advanced lower rectal cancer (LARC).

We performed microscopic observations of three female cadavers using India ink into the submucosa at the dentate line (DL) of the cadaver. We examined the clinical outcomes of 74 patients with LARC who underwent total mesorectal excision after preoperative treatment, classifying them as anterior (A), lateral (L), or posterior (P) based on the deepest part of the tumor.

Two of the three anterior walls contained the Denonvilliers' fascia (DVF), and the DVF became indistinct at the height of DL, where India ink extended to the vagina via the perivascular space and was absorbed into the vaginal lymph vessels. One case did not have DVF, and lymph vessels in the rectum distributed in close proximity to vagina. On the lateral posterior wall, the ink spread extensively from DL and the front of the levator ani muscle, whereas on the posterior wall, lymph vessels containing absorbed ink were observed from the hiatal ligament to the front of the sacrum. In the survival analysis, the 3-year disease-free survival rates were 71.9%, 100%, and 69.7% for A, L, and P groups, respectively, with a higher recurrence rate in the anterior and posterior walls.

Lymphatic network beyond fascia around anorectum was spread to a specific route by location. The anatomical diversity of this network was thought to be involved in the poor outcome for LARC.

Myxofibrosarcomas (MFS) are highly infiltrative soft tissue sarcomas that most commonly occur in adults within the sixth to seventh decades. Diagnosis relies on histopathological analysis as no definitive molecular markers have been identified. This study seeks to describe the mutational landscape of MFS, characterize mutations unique to certain populations, and identify mutations that may be of particular utility in diagnosis and treatment.

Using the AACR Project GENIE database, we identified a cohort of 202 patients with MFS. Patients were stratified by sex, age, race, and ethnicity. Tumors were categorized as primary, metastatic, locally recurrent, or distant organ metastases. Somatic mutations and copy number alterations were identified. Data were analyzed using R and RStudio, with p<0.05 denoting statistical significance.

We are the first to link the following mutations to MFS: NOTCH3, ALOX12B, SDHA, ETV6, NCOA2 and SOS2. The most common somatic mutations included TP53 (27.98%), ATRX (14.68%), NF1 (9.17%), and RB1 (7.80%). Homozygous deletions were most frequent in TP53 (28.7%), CDKN2A (20.5%), CDKN2B (19.48%), and RB1 (15.38%), while amplifications were most frequent in NCOR1 (6.29%) and FLCN (5.13%). Several mutations frequently co-occurred, while NF1 and RB1 demonstrated total mutual exclusivity. NCOA2 mutations were exclusive to White patients and NKX2-1 to non-White patients. Mutations in MAP2K4 and ALOX12B were unique to males, while SDHA mutations were unique to females.

As we enter the era of precision medicine, classifying cancers by molecular markers will become increasingly valuable. Our investigation enriches the literature by identifying novel mutations and mutations exclusive to certain demographic groups. These findings support a shift beyond histology toward molecularly informed diagnostics and pathway-directed therapeutic hypotheses for MFS. Next steps should validate candidate markers in independent cohorts and link genomic profiles to clinicopathologic features, disease course, and treatment response to improve clinical translation. These observations will help shape diagnostics and targeted therapies against MFS.

Predicting programmed death-ligand 1 (PD-L1) expression in resectable lung cancer cases is highly significant for establishing treatment strategies. Although there were differences in tumor characteristics between central and peripheral lesions in non-small cell lung cancer (NSCLC), the relationship between tumor location and PD-L1 expression status has not been examined. We investigated the relationship between clinical background factors, including tumor location, and PD-L1 expression status.

A total of 245 NSCLC patients whose tumors were measuring 3 cm or less in diameter and had a consolidation tumor ratio (CTR) <0.5 were included in this study. A tumor was classified as peripheral if its location was in the outer one-third of the computed tomography horizontal section, and as central otherwise. PD-L1 immunohistochemistry was performed using 22C3 antibody. PD-L1 expression status were categorized as negative [PD-L1 tumor proportion score (TPS) <1%] and as positive (PD-L1 TPS ≥1%).

Statistically significant differences were identified in CTR (p=0.006), histology type (p<0.001) and tumor location (p=0.036) according to the PD-L1 expression status. A greater proportion of patients with a smoking history were observed in the PD-L1 expression positive group (p=0.076). Multivariate analysis revealed 0.94< CTR (p=0.033), non-adenocarcinoma (p=0.018) and central lesion (p=0.034) were independent predictive factors for positive PD-L1 expression status. A predictive scoring system incorporating these three factors demonstrated a stepwise increase in PD-L1 positivity with higher scores.

PD-L1 expression status significantly correlated with CTR, histological type and tumor location. This is the first report demonstrating a significant correlation between PD-L1 expression and tumor location in NSCLC. We believe that differences in the cancer microenvironment based on tumor location influence PD-L1 expression status in cancer cells.

This review surveys scientific literature published mainly during the past five years to compile information on the anti-glioma activities of various flavonoid groups, with particular attention to structural modifications in flavonoids, isoflavonoids, and neoflavonoids.

This review is based on selective literature searches in scientific databases, mainly PubMed and Scopus.

Optimal lipophilicity is probably important for flavonoid action in lipidic tissues of the brain. Many studies on flavonoids have shown that their biological activity and pharmacophore depend on the presence of three rings, one of which is heterocyclic with an oxygen atom. This ring is formed by the connection between rings A and B and is essential for the pharmacophore structure. Its shortening in iso- and neo-flavonoids results in a decreased concentration of these compounds in natural sources and possibly a decreased biological activity. Various hydroxyl groups and other substituents do not alter the basic pharmacophore structure but contribute to changes in biological activities, resulting in the inhibition of many enzymes or signaling pathways by individual flavonoids.

In general, because of the variation in the structure, flavonoids are capable of interacting with a high number of biological targets. As a result, a compound or compounds with high anti-glioma activity may be discovered.

The prognostic impact of the timing of adjuvant chemotherapy initiation in patients with resected pancreatic cancer is unclear. Therefore, this study aimed to investigate whether delayed initiation of S-1 adjuvant chemotherapy affects the survival of patients with resectable pancreatic cancer.

Patients who received S-1 adjuvant chemotherapy after undergoing R0/R1 resection were grouped according to whether adjuvant chemotherapy was initiated <60 (n=36) or ≥60 days (n=27) after surgery. Correlations between the time to chemotherapy initiation, clinicopathological factors, and survival were analyzed.

The median and mean times to chemotherapy initiation were 58 and 61 days, respectively. The delayed group had worse 2-year overall (57% vs. 80%, p=0.032) and recurrence-free survival (35% vs. 54%, p=0.044) rates than the early group. These results were similar in patients who completed S-1 adjuvant chemotherapy. In multivariate analysis, delayed initiation of chemotherapy, R1 resection, and tumor size (≥40 mm) were independent prognostic factors for poor overall survival. The delayed group had more patients with severe postoperative complications (Clavien-Dindo grade ≥III) (30% vs. 8%, p=0.028) and delayed recovery of serum albumin levels (postoperative days 7, 14, and 30: p=0.040, 0.004, and 0.003, respectively) than the early group.

Delayed initiation of S-1 adjuvant chemotherapy had an adverse impact on survival and was correlated with severe postoperative complications and delayed recovery of postoperative nutritional status.

Lenvatinib, a multikinase inhibitor, has shown potential anti-tumor activity in various cancers. This study evaluated its efficacy, safety, and apoptotic mechanisms in colorectal cancer (CRC) using HT-29 xenograft-bearing mice.

Mice were treated with lenvatinib at 0, 10, or 20 mg/kg for 20 days. Tumor growth, serum biochemistry, and histopathology were assessed. Protein expression related to ERK signaling and apoptosis was analyzed using immunohistochemistry.

Lenvatinib significantly suppressed CRC tumor growth, delaying progression up to 14-fold compared with controls. No body-weight loss or hepatic/renal toxicity was observed, indicating good tolerability. Mechanistically, lenvatinib reduced phosphorylated ERK and anti-apoptotic proteins (BCL-2, c-FLIP, XIAP) by 30-50%, while enhancing cleaved caspase-3, -8, -9, BAX, and BAK expression by 1.2-1.5-fold, promoting apoptosis.

Lenvatinib exhibits potent anti-CRC activity with minimal systemic toxicity. Its therapeutic effects are mediated through ERK pathway inactivation, suppression of anti-apoptotic proteins, and induction of caspase-dependent apoptosis.

Urine cyclic guanosine monophosphate (cGMP) has been proposed as a prognostic biomarker for therapy response and the risk of relapse of cervical cancer after treatment with radiotherapy (RT). In the present study, an in vitro model with cervical cancer cells (C4-1) was established to determine whether changes in extracellular cGMP levels were predictive for effects of ionization radiation (IR).

During exponential growth, C4-1 cells were exposed to IR with doses between 2 and 12 Gy. The cells were harvested at intervals between one and six days.

The effect of IR on cell growth and extracellular cGMP levels was dose- as well as time-dependent. Three and six days after IR, the cell fractions were reduced with identical sensitivity (ED50 of 1.9 and 1.8 Gy, respectively). The extracellular cGMP levels showed a fall from the first day to sixth day, both in control and after irradiation (2 and 4 Gy), but with somewhat higher levels after IR. However, the extracellular cGMP levels increased after 8 and 12 Gy exposure by 100% and 270%, respectively. When the data were presented as extracellular cGMP levels (% above control), a clear dose- and time-dependency were observed.

From a translational perspective, extracellular cGMP levels may be used to monitor effects and be a potential tool for individualization of radiation therapy (RT).

Soft tissue concerns are common, yet most primary care physicians must refer patients to radiology for further imaging, leading to potential delays in diagnosis and management. Point-of-care ultrasound (POCUS) is increasingly available in primary care and has been shown to improve clinical decision making. However, current Family Medicine POCUS curricula focus primarily on cellulitis and abscess, overlooking other common soft tissue pathologies. This study aims to evaluate the frequency of soft tissue pathologies and associated follow-up recommendations on comprehensive radiology ultrasound exams ordered by Family Medicine physicians.

A retrospective study of radiology-performed comprehensive ultrasound exams ordered by an academic urban Family Medicine practice over the course of the 2019 was performed. Data collected included patient demographics, ultrasound findings, anatomic location, and follow-up recommendations. Diagnoses were categorized, and time from order to completion was calculated.

Soft tissue ultrasounds comprised 10% (n = 168) of all ultrasound studies ordered. The most common diagnosis were lymph nodes, n = 44 (25%), lipomas n = 32 (18%), and no lesion/normal n = 23 (13%). Only 2 studies diagnosed abscess (1%). The median time from order date to completion was 6 days (IQR 2 to 22 days), with 48% waiting over a week. Half (51%) of studies required no further follow up, while 26% required additional imaging or biopsy.

These findings highlight the need for expanded Family Medicine POCUS training to include high-yield diagnoses such as lipomas, lymph nodes, and cysts. POCUS could reduce unnecessary referrals, expedite care, and improve diagnostic confidence. Future research should explore primary care-specific POCUS protocols and their impact on patient outcomes.

Deep learning (DL) reconstruction methods have shown promise in accelerating 2D MRI sequences but have yet to be extensively validated for routine 3D volumetric MRI applications. Our purpose was to assess the diagnostic quality of a novel DL-accelerated 3D T1-MPRAGE compared with a state-of-the-art wave-controlled aliasing in parallel imaging (Wave-CAIPI) accelerated 3D T1-MPRAGE for evaluating intracranial enhancing lesions.

This prospective study was approved by the Institutional Review Board. Patients undergoing contrast-enhanced brain MRI in an outpatient setting were scanned on 3T MRI systems. The imaging protocol included a state-of-the-art Wave-CAIPI postcontrast T1-MPRAGE (acceleration factor [R] = 2 × 2, acquisition time [TA] = 2:11 minutes) and a research-based postcontrast DL-T1-MPRAGE (R = 2 × 2, TA = 2:11 minutes). The DL-based reconstruction process involved 2 steps. The first step, inspired by variational networks, involved 6 iterations alternating between data consistency updates and neural network evaluation. The second step applied a super-resolution algorithm for further image enhancement. Two independent neuroradiologists conducted a blinded, randomized head-to-head comparison of the 2 sequences by using a previously published scale across the following criteria: visualization of dural, parenchymal, leptomeningeal, and ependymal enhancement; sharpness; noise; artifacts; and overall diagnostic quality. A third board-certified neuroradiologist adjudicated cases with discrepant ratings. Noninferiority of DL-T1-MPRAGE was tested by using a 15% margin.

A total of 115 patients (68 women/47 men, mean age = 54 ± 10 years) were included. The top 3 clinical indications were: neoplasm (52%), vascular lesions (24%), and headache (8%). DL-T1-MPRAGE was noninferior to Wave-CAIPI T1-MPRAGE for delineating enhancing lesions with unanimous agreement in all cases with enhancing pathology. It was also noninferior in terms of noise perception (P < .0001), artifact (P < .0001), sharpness (P = .001), and overall diagnostic quality (P < .0001). DL-T1-MPRAGE provided equivalent visualization of small, subtle enhancing parenchymal, dural, and leptomeningeal lesions.

The highly accelerated postcontrast DL-T1-MPRAGE demonstrated noninferior image quality compared with the clinically validated Wave-CAIPI T1-MPRAGE accelerated sequence while offering enhanced visualization of subtle enhancing lesions.