Cancers最新文献

Background: Prostate cancer (PCa) accounts for 22% of the new cases diagnosed in Hispanic/Latino (H/L) men in the US. PCa has the highest incidence (38.3%) and mortality (16.4%) among all types of cancer diagnosed in Puerto Rico. We previously showed that PCa patients (n = 41) have a significant reduction of 59% in their levels of DNA repair capacity (DRC) when compared to controls (n = 14). This study aimed to evaluate DRC levels through the nucleotide excision repair (NER) pathway for the first time in 16 Puerto Rican H/L men with metastatic castration-resistant PCa (mCRPCa) while establishing comparisons with controls and PCa patients with indolent and aggressive disease.

Methods: Blood samples and clinicopathological data from PCa cases (n = 71) and controls (n = 25) were evaluated. PCa cases were stratified into mCRPCa (n = 16), aggressive (n = 31), and indolent (n = 24). DRC levels through NER were measured in lymphocytes with the CometChip assay. The stratification by Gleason score (GS) was GS6 (n = 7), GS7 (n = 23), GS ≥ 8 (n = 20), and mCRPCa patients (n = 16).

Results: Significant statistical differences were found when comparing the DRC values of the controls with any other of the four PCa patient groups. mCRPCa patients had the lowest mean DRC level of all four patient groups studied. The mean DRC level of mCRPCa patients was 6.65%, and compared to the controls, this represented a statistically significant reduction of 62% (p < 0.0001). Further analysis was performed to evaluate the contributions of age, anthropometric measurements, and prostate-specific antigen (PSA) levels to the DRC. Kaplan-Meier curves of mCRPCa revealed that survival probability decreased by approximately 50% by 30 months. This pilot study uses a blood-based phenotypic assay to present the first report of mCRPCa in Puerto Rican men and at a global level of DRC levels of mCRPCa patients.

Conclusions: This study evaluated DRC levels through the NER pathway for the first time in 16 Puerto Rican H/L men with mCRPCa. Significant differences in DRC values were found between the controls and the three PCa patient groups. Kaplan-Meier curves revealed that survival probability decreased by approximately 50% by 30 months, and only 20% of the cohort was alive at 50 months, confirming the lethality of mCRPCa in this H/L population. This pilot study represents the first report of metastatic PCa in Puerto Rican men at a global level of DRC levels of mCRPCa patients using a blood-based phenotypic assay.

Background/Objectives: Resection of tumors invading the cavernous sinus (CS) carries a risk of injury to the cranial nerves and internal carotid artery. Therefore, radical surgery involving lesions around the CS remains challenging, especially for lesions invading the CS, optic sheath, and oculomotor cave. Here, we describe a surgical strategy for meningiomas invading these structures and report on the clinical outcomes. Methods: Surgical resection was indicated in patients with neurological symptoms or rapid tumor growth for the restoration of cranial nerve function. We investigated 13 patients who had preoperative images of CS invasion, underwent surgical resection, and were followed-up with magnetic resonance imaging for at least 1 year between July 2017 and July 2024. Their preoperative symptoms, postoperative course, adjuvant therapy, postoperative complications, degree of resection, and recurrence were evaluated. Results: The mean patient age was 59.1 years (range, 23-73 years), and 10 were female. Major preoperative symptoms included oculomotor nerve paresis in 8 patients (61.5%), abducens nerve paresis in 6 (46.2%), visual disturbance in 7 (53.8%), and brain swelling in 3 (23.1%). These symptoms improved at least partially after surgery in 7 (87.5%), 5 (83.3%), 7 (100%), and 3 (100%) patients, respectively. Major postoperative complications included contralateral visual deterioration in 1 patient (7.7%) and brief transient slight hemiparesis caused by internal carotid vasospasm or dissection in 2 (15.4%). Four patients with residual atypical meningioma in the CS underwent intensity-modulated radiotherapy (IMRT). The lesions in 6 patients recurred or regrew, resulting in additional treatment with stereotactic radiosurgery in 2 patients, IMRT in 3, and resection in 1. Conclusions: Our surgical strategy for the surgical resection of meningiomas in and around the CS for the restoration of cranial nerve function is safe and effective, with only transient acceptable injuries. Even if the tumor in the CS is too stiff to be removed, it is important to open the optic nerve sheath and oculomotor cave widely to effectively remove the tumor.

Whole-body magnetic resonance imaging (WB-MRI) is being employed with increasing frequency to evaluate a broader spectrum of patients with diverse types of cancer and for cancer screening purposes. While clinical guidelines support its use, a standardized radiological approach is still lacking. To improve consistency in the acquisition, interpretation, and reporting of WB-MRI examinations, three reporting and data systems (RADSs) have been recently suggested: METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P), Myeloma Response Assessment and Diagnosis System (MY-RADS), and Oncologically Relevant Findings Reporting and Data System (ONCO-RADS). MET-RADS-P was developed to stage and monitor men with advanced prostate cancer using WB-MRI. It has emerged as a reliable imaging biomarker for predicting metastatic disease progression and assessing treatment response. MY-RADS was developed to stage and monitor patients with multiple myeloma using WB-MRI, emerging as a prognostic imaging biomarker. However, the evidence regarding inter-reader agreement for MY-RADS is currently limited. ONCO-RADS was developed to standardize the use of WB-MRI for cancer screening in individuals with cancer predisposition syndromes and in the general population. While initial findings are promising, the evidence supporting its use remains limited. To further validate and expand upon these promising preliminary findings, additional large-scale, prospective, multicenter studies are necessary.

Background/Objectives: The EndoPredict^® assay has been widely used in recent years to estimate the risk of distant recurrence and the absolute chemotherapy benefit for patients with estrogen (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, there are no well-defined criteria for selecting patients who may benefit from the test. The aim of this study was to develop a novel nomogram to estimate the probability of obtaining a high-risk EndoPredict^® result in clinical practice. Methods: The study cohort comprised 348 cases of T1-3/N0-1a/M0 ER-positive/HER2-negative breast carcinoma. A multivariate analysis was conducted using a training cohort (n = 270) based on clinicopathological features that demonstrated a statistically significant correlation with the EndoPredict^® result in a univariate analysis. The predictive model was subsequently represented as a nomogram to estimate the probability of obtaining a high-risk result in the EndoPredict^® assay. The predictive model was then validated using a separate validation cohort (n = 78). Results: The clinicopathological features incorporated into the nomogram included tumor size, tumor grade, sentinel lymph node status, pN stage, and Ki67. The internal validation of the model yielded an area under the curve (AUC) of 0.803 (95% CI = 0.751, 0.855) in the receiver operating characteristic (ROC) curve for the training cohort, with an optimal sensitivity and specificity at a threshold of 0.536. The external validation yielded an AUC of 0.789 (95% CI = 0.689, 0.890) in its ROC curve, with optimal sensitivity and specificity achieved at a threshold of 0.393. Conclusions: This study presents, for the first time, the development of a clinically accessible nomogram designed to estimate the probability of obtaining a high-risk result in the EndoPredict^® assay. The use of easily available clinicopathological features allows for the optimization of patient selection for the EndoPredict^® assay, ensuring that those who would most benefit from undergoing the test are identified.

The HOX gene family encodes for regulatory transcription factors that play a crucial role in embryogenesis and differentiation of adult cells. This highly conserved family of genes consists of thirty-nine genes in humans that are located in four clusters, A-D, on different chromosomes. While early studies on the HOX gene family have been focused on embryonic development and its related disorders, research has shifted to examine aberrant expression of HOX genes and the subsequent implication in cancer prediction and progression. Due to their role of encoding master regulatory transcription factors, the abnormal expression of HOX genes has been shown to affect all stages of tumorigenesis and metastasis. This review highlights the novel role of the HOX family's clinical relevance as both prognostic and diagnostic biomarkers in hematological and solid tumors.

Pathway inhibitors targeting Bruton tyrosine kinase (BTK) and B-cell lymphoma-2 (BCL-2) have dramatically changed the treatment landscape for both treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL). However, with increased utilization, a growing number of patients will experience progressive disease on both agents. This subgroup of "double refractory" patients has limited treatment options and poor prognosis. Chimeric antigen receptor (CAR)-T cells have transformed the treatment of relapsed/refractory B-cell malignancies. Although the earliest success of CAR-T cell therapy was in CLL, the clinical application of this modality has lagged until the recent approval of the first CAR-T cell product for CLL. In this review, we describe the current treatment options for upfront and subsequent therapies and the unmet need for novel agents highlighted by the burgeoning role and challenges of CAR-T cell therapy.

Background: Growing evidence attests to the multifaceted roles of group 2 innate lymphoid cells (ILC2s) in cancer immunity. They exhibit either pro- or anticancer activity depending on tumor type but their function in Multiple Myeloma (MM) is still not elucidated.

Methods: The bone marrow (BM) and peripheral blood (PB) of patients (pts) with MM or precancerous conditions were collected, and specific properties of ILC2 subsets were assessed by flow cytometry.

Results: By dissecting ILC2s according to c-Kit marker, we observed that NKp30 and NKG2D were mainly confined to c-Kit^hi ILC2s, while levels of DNAM-1 was significantly higher in fully mature c-Kit^lo cells. Among the total MM-associated ILC2s (MM-ILC2s), we observed a significant increase in c-the Kit^lo subset, but the expression of DNAM-1 in these cells was significantly reduced, especially in BM. Interestingly, MM-ILC2s from PB expressed granzyme B (GZMB), but its expression was impaired in BM-ILC2s. Accordingly, MM cells were susceptible to killing by MM-ILC2s derived from PB while eluding ILC2 surveillance in BM. Indeed, in MM-ILC2s derived from BM, the downregulation of DNAM-1 is accompanied by the upregulation of TIGIT, which mediate cell death in ILC2s upon recognition of the cognate ligands expressed by MM cells. These ILC2 changes appeared in clinical precursor conditions and eventually accumulated with disease progression.

Conclusions: MM-ILC2s can act as cytolytic immune effectors that are fully competent in PB. However, MM cells shift ILC2 fate towards cell death in BM via the upregulation of TIGIT, thereby representing a potential therapeutic target to restore ILC2 antitumor activity.

Background: Renal cell carcinoma tends to invade venous structures, frequently extending beyond the inferior vena cava and into the heart itself, such as into the right atrium or right ventricle. Resection of tumor burden, particularly tumor thrombus, often requires cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), which is not feasible for all patients.

Methods: Described in this study is a novel, minimally invasive endovascular approach involving endovascular thrombectomy as a viable approach in these select patients.

Results: There were no surgical complications, shorter operating times, less blood loss and an average length of stay of 5.5 days in the four patients undergoing this procedure.

Conclusions: We demonstrate that this technique can eliminate the need for cardiac bypass and deep hypothermic cardiac arrest and its associated risks, thereby making surgery safer and more accessible for patients with advanced kidney cancers with an inferior vena cava tumor thrombus. Furthermore, it allows for this life-saving surgery to be carried out in medical centers or hospitals where cardiac surgery is unavailable, or when cardiopulmonary bypass is medically contraindicated.

Background: Since 2011, Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) has emerged as a promising treatment option for patients with peritoneal surface malignancies (PSM) who are not eligible for cytoreductive surgery (CRS). Repeated minimal-invasive treatment is one of the key features and the current empirical standard treatment (ST) consists of at least three administrations over about three months. However, many patients are unable to complete the full course, limiting the potential benefits of PIPAC. Method: This retrospective, single-center study assessed the completion rate of ST and identified the main causes and predictive factors for discontinuation. This study also evaluated the feasibility, safety, and efficacy of PIPAC and investigated whether improved patient selection over the years has resulted in better oncological outcomes. Result: Data from 168 patients treated with PIPAC between January 2017 and March 2023 for a total of 336 procedures showed that only 29% completed ST. Multivariate analysis identified ascites >500 mL and a prior history of bowel obstruction as significant predictors of discontinuation. Conclusions: Patients with radiological or clinical signs of obstruction should not be considered for PIPAC treatment, and ascites increases the risk of incomplete treatment. Larger studies are eagerly awaited to corroborate these findings and refine the selection criteria by disease entity.

Background: Cancer-associated fibroblasts have been reported to play a central role in driving cancer progression, promoting metastasis, and conferring resistance to therapy in HNSCC.

Methods: Indirect and direct co-culture models of HPV-positive and HPV-negative HNSCC cells with fibroblasts were developed to study the effect of fibroblasts on cancer cells. ELISA was used to measure IL-6 secretion in these models. To dissect the underlying signalling mechanisms, the effects of IL-6, an IL-6 receptor (IL-6R) inhibitor, a MAPK/ERK inhibitor, and a JAK/STAT inhibitor were evaluated. Epithelial-to-mesenchymal transition (EMT) was assessed by measuring EMT markers and conducting scratch assays and spheroid assays. Radioresistance was evaluated using clonogenic assays. Additionally, radioresistant (RR) cell lines were established from parental cells to examine the correlation between radioresistance and EMT.

Results: Fibroblasts were found to drive EMT-like changes and heightened radioresistance in HNSCC cells through IL-6 secretion. Remarkably, these Fb-driven effects were robustly reversed using IL-6R and MAPK/ERK inhibitors in both HPV-positive and HPV-negative cell lines, whereas JAK/STAT inhibitors proved effective only in HPV-negative cells. RR cell lines exhibit a more aggressive phenotype than their parental counterparts, marked by pronounced EMT features and heightened resistance to radiotherapy. Importantly, these aggressive characteristics were substantially attenuated by targeting IL-6R or MAPK/ERK pathways.

Conclusions: This study highlights the critical role of fibroblast-secreted IL-6 in driving and maintaining EMT and radioresistance in HNSCC, resulting in a more aggressive tumour phenotype. Targeting the IL-6/IL-6R/ERK pathway emerges as a promising therapeutic approach for combating CAF-driven tumour progression and improving clinical outcomes in patients with aggressive, therapy-resistant HNSCC.