Primary adenosquamous carcinoma of the prostate is an extremely rare and aggressive variant, accounting for less than 1% of all prostate cancers. Due to its rarity, the prognosis is poor, with no established treatment. Prostate-specific antigen levels are typically within the normal range in primary adenosquamous carcinoma of the prostate.

We present the case of a 57-year-old East Asian male in whom pathological and imaging findings led to the diagnosis of primary adenosquamous carcinoma of the prostate. His prostate-specific antigen levels were initially high and continued to increase rapidly thereafter to 161.89 ng/ml. Although hormonal therapy achieved a reduction in prostate-specific antigen levels, the disease progressed rapidly, with extensive metastases to multiple sites, including the lung, lymph nodes, pancreas, bone, and skeletal muscle as an extremely rare metastatic site. The patient died 6 months after diagnosis despite subsequent multidisciplinary treatment.

This patient with primary adenosquamous carcinoma of the prostate demonstrated rapid increase of prostate-specific antigen as an uncommon clinical feature. Further accumulation of cases is needed to understand and treat this rare and aggressive disease.

Limb amputation is a standard surgical procedure in dogs for the management of limb tumors such as osteosarcoma, soft tissue sarcoma, and malignant peripheral nerve sheath tumors. While many dogs adapt functionally to limb loss, altered biomechanics, compensatory strain on remaining limbs, and impaired mobility can negatively impact their quality of life. Physiotherapy is recommended to facilitate post-amputation recovery; however, objective data on its effectiveness in dogs remain limited. Furthermore, when radiotherapy is required postoperatively, the necessary daily anaesthesia and cage rest can exacerbate functional decline due to restricted activity. The impact of physiotherapy on gait function in a forelimb-amputee dog undergoing concurrent radiotherapy is described in this report.

A 14-year-old neutered male Toy Manchester Terrier underwent left forelimb amputation following the diagnosis of a malignant peripheral nerve sheath tumor at the C6-T1 spinal level. One month postoperatively, the dog began a three-week course of radiotherapy that required daily anaesthesia and prolonged cage rest, raising concerns about mobility deterioration. To mitigate these effects, a structured physiotherapy program was implemented. The program consisted of daily 30-minute sessions focusing on range of motion exercises, balance and proprioception training, weave pole exercises, and cavaletti rail walking. Gait analysis was performed on the first and last days of the physiotherapy program (pre- and post-physiotherapy) using a two-dimensional kinematic system. After three weeks of physiotherapy, a reduction in vertical head movement was observed (48.3 cm to 34.5 cm), indicating improved gait stability. Additionally, shoulder and elbow extension showed an increase during the loading response phase, which is crucial for weight-bearing and locomotor efficiency.

This case provides objective evidence supporting the potential benefits of physiotherapy in enhancing gait function and stability in dogs following a forelimb amputation, even when physical activity is restricted due to radiotherapy-related hospitalization. The findings suggest that integrating physiotherapy into post-amputation care may mitigate functional decline associated with prolonged cage rest and optimize recovery. Further studies are needed to investigate the long-term benefits of physiotherapy and effects of physiotherapy on compensatory musculoskeletal adaptations in amputee dogs.

Tongue squamous cell carcinoma (TSCC) is a common oral cancer that has a high propensity for recurrence and metastasis. Therefore, TSCC has a 50% 5-year survival rate. Platinum-based chemotherapy is an effective treatment for squamous cell carcinoma, however, chemotherapy resistance remains a major issue. Therefore, innovative and effective drug combinations are needed to improve TSCC patient prognosis.

In this study, we conducted an in vitro CRISPR/Cas9 library screen using two TSCC cell lines (Tscca and Cal27) to identify specific genes that, when inhibited, synergize with cisplatin to effectively suppress tumor growth.

We identified STK19 as a potential drug target. Inhibition of STK19 enhances the response of TSCC to cisplatin. Through genetic and pharmacological methods, it has been demonstrated that reducing STK19 activity enhances cisplatin-induced DNA damage. The mechanism involves the depletion of MGMT with STK19 inhibition, leading to conditional lethality and synergistic reduction of tumors in vivo when combined with cisplatin. Overall, in this study, unbiased genetic testing was used to successfully identify synthetic lethal drug combinations for TSCC.

STK19 was identified as a promising target that could enhance the killing effects of cisplatin on tongue squamous carcinoma cells, offering a novel therapeutic option for individuals who are insensitive to conventional treatment methods.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with limited treatment options and poor prognosis. Identifying novel molecular regulators is essential for improving therapeutic strategies. In this study, we identified Sortilin-related VPS10 domain-containing receptor 3 (SorCS3) as a novel tumor suppressor candidate in ACC.

Through expression detection and functional validation, we investigated the role of SorCS3, a member of the VPS10p-domain receptor family, in ACC. Expression data from TCGA and clinical tissue samples were analyzed. Endocytic activity, protein interactions, and downstream signaling were examined using immunofluorescence, co-immunoprecipitation (Co-IP), and western blotting in ACC cell lines.

SorCS3, previously regarded as CNS-specific, was detected in ACC tissues and cell lines. Low SorCS3 expression was associated with reduced overall survival (OS) and disease-specific survival (DSS). Functional assays showed that SorCS3 enhanced endocytosis and colocalized with early endosomes. Co-IP revealed a physical or indirect interaction between SorCS3 and Insulin-like growth factor 2 receptor (IGF2R), a multifunctional receptor involved in IGF-II degradation and signal attenuation. SorCS3 overexpression (OE-SorCS3) increased IGF2R protein levels and suppressed PI3K/Akt and MAPK/Erk signaling. Blocking endocytosis partially reversed these effects, supporting a receptor trafficking-dependent mechanism.

In this study, we identified SorCS3 as a novel tumor suppressor candidate in ACC. Although previously thought to be CNS specific, SorCS3 was found to be expressed in ACC tissues and cell lines. Low SorCS3 levels correlated with poor patient survival in the TCGA cohort. Functionally, SorCS3 enhanced endocytosis in ACC cells and physically or indirectly interacted with IGF2R. OE-SorCS3 increased IGF2R protein levels and reduced phosphorylation of Akt/Erk, suggesting tumor-suppressive effects through IGF2R stabilization and signaling inhibition. Overall, our findings highlight the SorCS3-IGF2R axis as a previously unrecognized regulatory mechanism in ACC progression and suggest that receptor trafficking could be a viable therapeutic target in this malignancy.

Myeloid/Lymphoid Neoplasms (MLN) with eosinophilia and PDGFRB rearrangements are rare but distinct hematologic malignancies driven by the constitutive activation of the PDGFRB tyrosine kinase through gene fusions. These neoplasms are sensitive to tyrosine kinase inhibitors (TKIs) such as imatinib, which often leads to rapid and durable molecular remissions. However, diagnostic challenges frequently arise from cryptic rearrangements, necessitating comprehensive molecular approaches.

A 37-year-old male patient initially presented with pancytopenia and a splenic infarct; subsequent bone marrow findings were suggestive of a myeloid/lymphoid neoplasm. Initial conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) identified a PDGFRB gene rearrangement but were unable to fully resolve the structural complexity of the underlying genomic alteration. Long-read sequencing helped resolve a complex three-way translocation involving chromosomes 5, 12, and 20, precisely defining the ETV6::PDGFRB fusion with base pair resolution, and identified the partner gene (KAT14) on chromosome 20p. Following the diagnosis, the patient was started on imatinib therapy and has since achieved clinical and hematological improvement.

This case highlights the significant diagnostic utility of long-read sequencing in uncovering and characterizing cryptic and complex genomic rearrangements that are frequently missed by conventional methods. Accurate molecular characterization is critical for disease classification, guiding targeted therapeutic decisions, and ultimately improving patient outcomes in PDGFRB-rearranged neoplasms.

Metronomic chemotherapy shows potential to enhance efficacy of PD-1 antibodies but has not been assessed in gastrointestinal (GI) cancer. Immunotherapy efficacy can be affected by body composition and lipid metabolism of patients. We aimed to evaluate the feasibility of metronomic capecitabine plus camrelizumab as a salvage treatment of late-stage GI cancer and to explore the roles of body composition and lipid metabolism in this regimen.

This is a single-center, exploratory trial. Eligible GI cancer patients who had disease progression after standard chemotherapy were treated with metronomic capecitabine (500 mg twice daily) plus camrelizumab (200 mg on day 1 intravenously every 2 weeks). The primary endpoint was safety. Body composition indices analyzed by SliceOmatic software and lipidomics analyses using liquid chromatography-mass spectrometry were performed as exploratory investigation. Differentially expressed genes (DEGs) of C2C12 myocytes treated with metronomic dose 5-fluorouracil were detected by RNA sequencing.

A total of 26 patients were enrolled. Treatment emergent adverse events (TEAEs) grade ≥ 3 occurred in five patients (19.2%). Objective response rate was 19.2% (5/26), including two patients with complete response. High skeletal muscle radiation attenuation (SMRA) was associated with disease control and better survival. Differential plasma lipids were identified in disease-controlled patients compared with those who showed disease progression. High levels of a 6-lipid signature composed of SM40:1;3, TG54:4-FA20:2, LPC(16:0), TG52:0-FA20:0, TG56:3-FA20:2, and PE(P-18:1/18:2) were associated with better survival. SMRA and this plasma lipid panel were both increased in disease-controlled patients after treatment. DEGs including prkg1, adora1, and Il15 in metronomic 5-FU treated C2C12 myocytes could be enriched into lipid metabolism pathways.

Metronomic capecitabine plus camrelizumab is well tolerated and shows promising efficacy in GI cancer. SMRA and specific plasma lipids are associated with efficacy of this regimen and indicate the modulation effect of metronomic capecitabine on lipid metabolism.

NCT04508686 (Aug 11, 2020), NCT04510818 (Aug 12, 2020), NCT04932187 (Sep 17, 2021).

This research aimed to assess the efficacy and safety of a regimen combining lenvatinib with an anti-PD-1 antibody or chemotherapy in patients with advanced intrahepatic cholangiocarcinoma (ICC).

A two-arm, open-label, phase II trial was carried out. Participants in Arm A received 240 mg of toripalimab intravenously on day 1 of each 3-week cycle, plus daily oral lenvatinib at 8 mg (< 60 kg) or 12 mg (≥60 kg). Participants in Arm B were administered the same daily lenvatinib in combination with GEMOX chemotherapy: 85 mg/m² oxaliplatin on day 1, and 1 g/m² gemcitabine on days 1 and 8 every 3 weeks for 6-8 cycles. The primary endpoint was the objective response rate (ORR) per RECIST 1.1, with secondary endpoints included treatment-related adverse events (AEs), overall survival (OS), and progression-free survival (PFS).

Sixty one patients were recruited, with 31 in Arm A and 30 in Arm B. The ORR of Arm A was 32.3% (10/31; 95% CI: 16.7%-51.4%), and three patients underwent surgery after tumor downstaging. The median OS was 20.3 months (95% CI: 9.3-27.1), and median PFS was 8.9 months (95% CI: 4.2-13.9). Arm B showed an ORR of 40.0% (12/30; 95% CI: 22.7%-59.4%), and one patient proceeded to surgery after downstaging. Median OS was 15.5 months (95% CI: 9.6-23.8), and median PFS was 8.0 months (95% CI: 5.0-11.4). Adverse events (AEs) related to treatment were observed in most patients, with grade 3-4 AEs in 35.5% of Arm A and 40.0% of Arm B. The most frequent AEs were fatigue (71% vs. 63%), paresthesia (45% vs. 40%), and gingivitis (45% vs. 20%). Grade 4 thrombocytopenia occurred in 6.7% of Arm B. No grade 5 AEs were observed. Peripheral blood analysis showed monocyte levels decreased in PR(partial  response) patients in Arm A but increased in PR patients in Arm B.

The Combination of lenvatinib with either anti-PD-1 antibody or GEMOX chemotherapy is a well-tolerated and effective treatment for advanced ICC.

ClinicalTrials.gov, NCT04361331.

SMARCA4-deficient cervical adenocarcinoma is an exceedingly rare and aggressive subtype of cervical malignancy that presents with clinicopathological features mimicking other types of cervical cancer, leaving no established treatment protocols available. This report describes a case of a 50-year-old woman in perimenopause who presented with an increase in vaginal discharge, discomfort in the external genitalia, and bleeding after intercourse. The imaging examination revealed a cervical mass accompanied by enlarged lymph nodes in the pelvic cavity. A cervical biopsy confirmed adenocarcinoma, with an initial clinical stage classified as International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIA1. The patient underwent a radical hysterectomy and pelvic lymph node dissection (PLND), during which it was found that the tumor had involved pelvic lymph nodes. The revised staging was Stage IIIC1. According to the postoperative pathologic analysis, the woman was diagnosed as adenocarcinoma with a poorly differentiated grade and with myoepithelial differentiation features. Immunohistochemical analysis supported the diagnosis of the SMARCA4-deficient adenocarcinoma that was accompanied by high-grade squamous intraepithelial lesion (HSIL) in its surroundings, indicating the presence of two distinct types of lesions. Postoperative review after one month revealed multiple lymph node metastases in the left neck. Pathological examination confirmed it as distant metastasis from cervical adenocarcinoma, ultimately leading to a diagnosis of pT1N1M1 (IVB stage) cervical cancer. Following a six-cycle treatment regimen with cadonilimab, paclitaxel, and cisplatin, the lymph nodes in the neck demonstrated a significant reduction, indicating a preliminary positive response. In this case, SMARCA4-deficient cervical adenocarcinoma was characterized by significantly high invasive potential, early metastasis, and heterogeneity, indicating the significance of early detection and molecular pathological diagnosis in guiding personalized treatment strategies. Immunotherapy combined with chemotherapy may offer a new therapeutic approach for this rare type of cancer.

Cervical cancer (CC) remains a formidable clinical challenge, particularly in advanced stages where immune checkpoint blockade yields suboptimal responses. Despite the established role of the tumor microenvironment (TME) in fostering immunosuppression, the precise mechanisms of stroma-immune crosstalk in CC remain elusive. Leveraging single-cell RNA sequencing of 77,221 cells from CC and normal cervical tissues, we uncovered a tumor-enriched subpopulation of inflammatory cancer-associated fibroblasts (iCAFs) marked by elevated CD54 expression (CD54⁺ iCAFs), which independently predicted adverse clinical outcomes. Systematic dissection of intercellular communication networks revealed a tumor-specific alliance between CD54⁺ iCAFs and ITGAL⁺ macrophages, orchestrated through dysregulated ligand-receptor signaling. Spatial multi-omics approaches, including multiplex immunohistochemistry and spatial transcriptomics, confirmed their colocalization within an immunosuppressive niche. Mechanistically, CD54⁺ iCAFs promote immunosuppression by polarizing ITGAL⁺ macrophages toward an M2-like phenotype, primarily via CCL2 secretion. These fibroblasts further support immune evasion through two complementary pathways: direct CD54-ITGAL contact-dependent signaling and soluble CCL2-mediated macrophage reprogramming. The resulting macrophage activation stimulates autocrine CXCL8 secretion and subsequent PD-L1 upregulation, which ultimately suppresses CD8⁺ T cell functions, fostering an immune-tolerant microenvironment in CC. Therapeutic intervention using the CXCL8-CXCR1/2 inhibitor reparixin disrupted the CXCL8-PD-L1 axis, reduced PD-L1⁺ macrophage abundance and enhanced CD8⁺ T cell cytotoxicity. Notably, combination therapy with PD-L1 blockade demonstrated synergistic efficacy. Collectively, our findings reveal a stromal-immune checkpoint axis orchestrated by CD54⁺ iCAFs and ITGAL⁺ macrophages that underpins immunosuppression in CC, thereby providing a translational rationale for stroma-directed combination therapies that may overcome resistance to current immunotherapies.

This case report describes an uncommon Mycobacterium avium infection mimicking lymphoma in a dog.

A 1.5-year-old female Miniature Schnauzer presented with persistent lymphadenopathy, fever, and diarrhea, which were refractory to conventional therapy. Hematological and biochemical analyses revealed anemia, thrombocytopenia, elevated liver enzymes, creatine kinase, glutamate dehydrogenase, lactate dehydrogenase, hyperkalemia, low IgG levels, and euthyroid sick syndrome. Ultrasonography confirmed generalized visceral, retroperitoneal, and peripheral lymphadenopathy with concurrent inflammatory reactions, splenomegaly, and hepatomegaly characterized by heterogeneous parenchyma and multiple foci, further supporting the suspicion of lymphoma. However, cytological examination of an enlarged lymph node showed no evidence of lymphoma but revealed the presence of numerous bacilli suggestive of mycobacterial infection. Histopathological evaluation of a surgically excised lymph node similarly failed to confirm lymphoma. Mycobacterium avium was successfully cultured from the lymph node tissue and identified via the GenoType Mycobacterium CM test. Based on antimicrobial susceptibility testing, the initial therapeutic regimen of enrofloxacin, azithromycin, and rifampicin was modified to clarithromycin. Adjunctive treatments included blood transfusion, levothyroxine, prednisolone, omeprazole, sucralfate, parapoxvirus ovis, and soy phospholipids. Despite a temporary clinical improvement, the patient's condition progressively worsened, and the dog succumbed to the disease after three months.

This case underscores the importance of including Mycobacterium avium in the differential diagnosis of generalized lymphadenopathy, particularly in Miniature Schnauzers. The findings support the routine use of Ziehl-Neelsen staining during cytological examinations to prevent misdiagnosis, especially in breeds predisposed to atypical infections. It also emphasizes the crucial role of targeted antimicrobial therapy in managing such cases, although the prognosis remains guarded.