Achieving optimal surgical margins is critical in breast-conserving surgery (BCS) to reduce local recurrence (LR) and the need for re-excision. This meta-analysis evaluated the impact of intraoperative margin optimization strategies on key surgical and oncologic outcomes in patients who underwent BCS.

Acral melanoma (AM) is the predominant subtype of melanoma in Asians. Early detection and prevention can significantly improve patient outcomes; however, there is a lack of effective early biomarkers for predicting AM metastasis. Here, we employed single-cell and spatial transcriptomics analyses to investigate early microsatellite lesions of AM and identify biomarkers of invasiveness in these lesions. Our results characterize a highly immunosuppressive microenvironment and metabolic process shifts in early AM microsatellite lesions that promote the metastatic potential. The transcription factor SOX6 is overexpressed in microsatellite lesions and marks a population of highly invasive melanoma cells. The pro-invasive role of overexpressed SOX6 was validated in vivo and in vitro, including its ability to enhance tumor invasion by upregulating cellular glycolysis, disrupt fatty acid transport, and increase intracellular phosphatidylcholine content. This study suggests that SOX6-overexpressing melanoma cells are the main driver subpopulation promoting early invasion of AM and establishes SOX6 and fatty acid transport processes as biomarkers and potential therapeutic targets for early melanoma metastasis.

Pathologically, intrahepatic cholangiocarcinoma (ICC) is classified into small-duct (SD) type and large-duct (LD) type, each with distinct clinicopathological characteristics. The contrast-enhanced ultrasound (CEUS) features of the two ICC types remain insufficiently explored.

Nutritional risk assessment indices impact disease prognosis, yet their prognostic roles in preoperative digestive system tumor (DST) patients remain unclear.

Accurate delineation of Gross Tumor Volume (GTV) in lung cancer is critical for effective radiotherapy and surgical planning. However, segmentation of GTV in high-resolution CT images remains challenging, particularly when tumors are small or have indistinct boundaries.

Conversion immunochemotherapy may enable curative surgery in patients with initially unresectable locally advanced gastric cancer, but its response rate remains low. Little evidence has shown how to easily predict therapeutic efficacy from hematological biomarkers, apart from tissue biomarkers. This study aimed to identify predictive factors for treatment response from hematological biomarkers and propose strategies for non-responsive patients.

Clinical studies demonstrate that comorbidity between colorectal cancer (CRC) and depression is common, leading to a higher mortality risk among CRC patients. However, the mechanisms remain largely unexplored. The role of core brain regions in comorbidity of CRC and depression and whether modulating these regions can improve both depression-like symptoms and CRC progression have yet to be clarified. In this study, we establish a mouse (Mus musculus) model of CRC and observe that mice with orthotopic colorectal cancer (CRC mice) display depression-like behaviors. Through c-FOS mapping, network analysis, correlation analysis, and inverse tracing, we identify the anterior cingulate cortex (ACC) as a central node within the depression-related brain network in CRC mice. Notably, inhibiting ACC activity not only alleviates depression-like behaviors but also mitigates CRC-induced neuronal damage and reduces CRC tumor progression. These findings underscore the critical role of the ACC in comorbidity of CRC and depression and suggest that ACC-targeted interventions may hold therapeutic potential for CRC patients with comorbid depression.

Local treatment of pelvic Ewing Sarcoma (EWS) is czhallenging due to complex anatomy and potential complications. Local therapy may be deferred to maintain chemotherapy dose-intensity, but the impact of this delay on outcomes remains unclear.

Breast cancer has become one of the most common malignant tumors in women, and the incidence rate is increasing annually in men. This study focused on exploring the prognostic significance of the combined detection of serum ALP and LDH in patients with breast cancer. We enrolled 80 individuals with male breast cancer (MBC), female breast cancers (FBCs) were randomly matched via propensity score matching (PSM). In the MBC cohort, the optimal cutoff values for ALP and LDH were determined to be 114 U/L and 207 U/L, respectively, whereas in the FBC cohort, they were 68 U/L and 133 U/L, respectively. There was a difference in median survival between patient groups classified by the optimal cutoff values of ALP and LDH in the FBC cohort. However, in the FBC cohort, there was no significant correlation between the levels of ALP or LDH and patient prognosis. We developed a "joint score" system that incorporates the values of both ALP and LDH and separates MBCs into three groups. Survival was significantly different among the three groups. In the multivariate analysis, the "joint score" was identified as an independent prognostic factor for both disease-free survival(DFS) and overall survival (OS).

Gastric MALT lymphoma diagnosis relies on histopathological findings and immunoglobulin H gene (IgHr) rearrangement testing, which reflects monoclonal immunoglobulin proliferation. This study aimed to clarify the role of IgHr in the diagnosis, treatment prediction, and surveillance of gastric MALT lymphoma. Of the 152 suspected cases, 131 were definitively diagnosed using a combination of IgHr and pathology, with pathological findings considered the gold standard. Patients with discrepancies between IgHr and pathology underwent re-evaluation. The relationship between IgHr status, clinicopathological features, and treatment outcomes was analyzed. IgHr and histopathology were assessed over 2 years in 41 patients after pathological complete remission (pCR). IgHr positivity was 69.5% at initial biopsy and 90.8% after two biopsies. IgHr-positive cases had higher H. pylori infection rates and better CR rates post-eradication. Patients with IgHr positivity at pCR had higher recurrence rates (16.7%). IgHr positivity gradually declined among 37 non-recurrent cases (CR: 56.8%, 6 M: 45.9%, 1Y: 21.6%, 2Y: 10.8%), indicating a delay between pCR and IgH-negative conversion. Repeated biopsies may improve the accuracy of gastric MALT lymphoma diagnosis. IgHr-positive status at pCR may signal higher recurrence risk, underscoring the need for careful post-CR surveillance. Surveillance should account for potential delays in IgHr-negative conversion.

Intratumoral low oxygen tension promotes cancer cell invasion and metastasis. Hypoxia-Inducible Factor 1-alpha (HIF1α) is the principal transcription factor orchestrating cellular responses to hypoxic stress, mediating the regulation of genes implicated in adapting to perturbations in oxygen homeostasis. Here, we describe our findings that functionally demonstrate a nucleolar localization domain in HIF1ɑ that enables HIF1ɑ to translocate to the nucleolus. Nucleolar HIF1ɑ binds the ribosomal DNA promoter and upregulates RNA Polymerase I activity leading to dysregulated ribosomal RNA transcription and consequently enhanced ribosome biogenesis. Ribosome biogenesis is important in supporting cellular metabolic processes and invasion and metastasis. Our findings are recapitulated in breast tumors wherein upregulated HIF1ɑ and rRNA biogenesis are associated with poor prognosis. Finally, our studies demonstrate that inhibition of RNA Polymerase I impedes aggressive traits of hypoxia-driven cancer progression, highlighting the potential of this approach as a therapeutic strategy in breast cancer. Cumulatively our work unravels an unprecedented role of HIF1ɑ in regulating rRNA biogenesis in breast cancer.

Recent evidence has highlighted immune checkpoint inhibitors as among the most promising immunotherapies for various malignancies. However, a significant proportion of HCC patients exhibit poor responses. Lipid metabolic heterogeneity is considered a key driver of cancer progression. However, the role of lipid metabolic reprogramming in HCC immunotherapy resistance remains poorly understood. Herein, we aimed to illuminate the potential relationship between lipid metabolic reprogramming and ICI resistance and provide novel strategies to increase the HCC immunotherapy response. Patients who received PD-1/PD-L1 inhibitors were enrolled. The effect of TACC3 on the tumor microenvironment was validated via single-cell RNA sequencing in HCC-bearing mouse models. Targeted metabolomics was performed to analyze the regulatory role of TACC3 in HCC metabolism. To address HCC immunotherapy resistance, we developed a targeted nucleic acid therapeutic utilizing N-acetylgalactosamine (GalNAc) to conjugate siTACC3. Through clinical cohort analysis, we found that TACC3 was overexpressed in HCC patients with poor response to immunotherapy. Furthermore, we demonstrated that silencing tumor-derived TACC3 optimizes the cytotoxicity of infiltrating CD8+ T lymphocytes. Both in vitro and in vivo assays suggested that TACC3 maintains ACSL4-mediated polyunsaturated fatty acid (PUFA) metabolism in HCC cells. Additionally, TACC3 accelerates ACSL4 expression by interacting with LARP1 and PABPC1, which stabilize ACSL4 mRNA. The results of preclinical models demonstrated the satisfactory efficacy of GalNAc-conjugated siTACC3 combined with PD-1 inhibitor therapy for HCC. In summary, tumor-derived TACC3 impairs the tumor-killing activity of CD8+ T lymphocytes through PUFA metabolism-associated crosstalk. Targeting TACC3 represents a novel and practicable strategy to augment ICI efficacy against HCC.

Mitosis is a critical phase of the cell cycle and a vulnerable point where cancer cells can be disrupted, causing cell death and inhibiting tumor growth. Challenges such as drug resistance persist in clinical applications. During mitosis, mRNA translation is generally downregulated, while non-canonical translation of specific transcripts continues. Here, we show that mitotic cancer cells redistribute ribosomes toward the 5' untranslated region (5' UTR) and beginning of the coding sequence (CDS), enhancing translation of thousands of upstream open reading frames (uORFs) and upstream overlapping open reading frames (uoORFs). This mitotic induction of uORF/uoORF enriches human leukocyte antigen (HLA) presentation of non-canonical peptides on the surface of cancer cells after mitotic inhibitor treatment. Functional assays indicate these epitopes provoke cancer-cell killing by T cells. Our findings highlight the therapeutic potential of targeting uORF/uoORF-derived epitopes with mitotic inhibitors to enhance immune recognition and tumor cell elimination.

Repeated oncogenic mutations and polyclonal proliferation are evident in cancers. However, little is known about the polyclonal principles governing the systemic cancerous lineage during immunotherapy. Here, we examine a unique autopsy case of metastatic urothelial carcinoma that exhibits different treatment responses to anti-PD-1 therapy at each tumor site. By performing in-depth analyses of different multiregional bulk tumor masses, we reveal that subsets of subclones acquire potential driver mutations under treatment selection pressure. Spatial transcriptomics analysis reveals that subclones resistant to immunotherapy form distinct immunosuppressive environments consistent with their habitats. Furthermore, different cancer hallmarks are identified in each of the subclones that expand under immunotherapy at single-cell level; for example, one subclone is more proliferative, and another is more stem-cell-like. In summary, this study provides an overall picture of the polyclonal competition and changes in the immune microenvironment that are related to resistance to immunotherapy in patients with malignancies.

Lymph node metastasis (LNM) is a crucial risk factor influencing an unfavorable prognosis in specific cancers. Fundamental research illuminates our understanding of tumor behavior and identifies valuable therapeutic targets. Nevertheless, the exploration of fundamental theories and the validation of clinical therapies hinge on preclinical experiments. Preclinical models, in this context, serve as the conduit connecting fundamental theories to clinical outcomes. In vivo models established in animals offer a valuable platform for comprehensively observing interactions between tumor cells and organisms. Using various experimental animals, including mice, diverse methods, such as carcinogen-induced tumorigenesis, tumor cell line or human tumor transplantation, genetic engineering, and humanization, have been used effectively to construct numerous models for tumor LNM. Carcinogen-induced models simulate the entire process of tumorigenesis and metastasis. Transplantation models, using human tumor cell lines or patient-derived tumors, offer a research platform closely mirroring the histology and clinical behavior of human tumors. Genetically engineered models have been used to delve into the mechanisms of primary tumorigenesis within an intact microenvironment. Humanized models are used to overcome barriers between human and murine immune systems. Beyond mouse models, various other animal models have unique advantages and limitations, all contributing to exploring LNM. This review summarizes existing in vitro and animal preclinical models, identifies current bottlenecks in preclinical research, and offers an outlook on forthcoming preclinical models.

T-cell activation and clonal expansion are essential to effective immunotherapy responses in non-small cell lung cancer (NSCLC). The distribution of T-cell clones may offer insights into immunogenic mechanisms and imply potential prognostic and predictive information.

Metastatic ovarian cancer patients who have recurrent disease after multiple lines of prior treatment have dismal prognosis. The Kristen rat sarcoma viral oncogene homologue (KRAS) G12C mutation is very rare in ovarian cancers and no approved KRAS G12C targeted treatment options exist for ovarian cancer. Here we present a case of metastatic ovarian serous adenocarcinoma in a female patient in her late 70s who was heavily pretreated with multiple lines of treatment before, showing an excellent durable response to KRAS G12C inhibitor sotorasib at reduced dose of 240 mg oral daily for over 26 months and ongoing. Our case highlights KRAS G12C as a driver mutation in ovarian cancer patients that is potentially targetable in certain subgroups of patients.

Cervical teratoblastoma in paediatric patients is an extremely rare and aggressive malignancy, with limited documentation in the medical literature. Teratoblastoma is a malignant variant of germ cell tumours, distinguished by its invasive growth pattern and poor cellular differentiation.A female child in early adolescence presented to our oncology hospital with complaints of persistent lower abdominal discomfort and abnormal uterine bleeding. These symptoms had been progressively worsening over time. On physical examination and imaging, pelvic ultrasonography and MRI revealed a complex cystic mass with hypoechoic features, located in the region between the cervix and the hymenal ring. Histopathological evaluation of a biopsy specimen confirmed the diagnosis of malignant cervical teratoblastoma. A multidisciplinary tumour board recommended surgical intervention. The patient underwent transvaginal excision of the cervical mass, with care taken to preserve reproductive anatomy.Postoperatively, adjuvant chemotherapy was initiated with the bleomycin, procarbazine (Natulan) and cisplatin regimen to reduce the risk of recurrence and metastasis. This case highlights the importance of early recognition, accurate diagnosis and a coordinated treatment approach in managing rare paediatric cervical malignancies.

Orbital metastasis is a rare manifestation of systemic malignancy, accounting for approximately 2%-5% of orbital tumours. The most common primary cancers associated with orbital metastases include breast carcinoma, malignant melanoma and prostate carcinoma. Hepatocellular carcinoma (HCC) is an uncommon source of all reported orbital metastases. We report the case of a man in his mid-50s with a history of alcoholic cirrhosis who presented with an acute onset of left periorbital pain, conjunctival injection, proptosis and restrictive ophthalmoplegia, in addition to abdominal discomfort. Orbital CT demonstrated a heterogeneously enhancing mass in the superolateral left orbit, associated with osseous erosion and displacement of adjacent orbital structures. Further imaging revealed multifocal hepatic lesions with evidence of portal vein invasion. A biopsy of the orbital mass confirmed metastatic HCC. The patient experienced rapid clinical deterioration before initiating treatment and ultimately passed away. This case highlights the importance of considering metastatic liver malignancy in the differential diagnosis of orbital masses, particularly in patients with risk factors for HCC.

This is a case of a man in his 60s initially diagnosed with gastric adenocarcinoma and treated with curative intent surgery and chemotherapy 6 years ago. Four years after initial treatment he had locoregional lymph node recurrence treated with curative chemoradiation and was on surveillance with no evidence of disease for 2 years. He presented to clinic with multiple 'bumps' on his head that had been increasing in size for the past 6 months. He has no other associated symptoms aside from 20 pounds of weight loss. The skin nodule was biopsied, and the pathology showed recurrence of his primary gastric adenocarcinoma. A positron emission tomography (PET)-CT showed a small area of metastasis in a single rib alongside this scalp lesion, without any areas of locoregional or intrathoracic recurrence. This is a rare case of cutaneous recurrence of primary gastric cancer without a high burden of intra-abdominal or visceral disease.