Metastatic Sites Research Articles

The inflammatory markers and locoregional pathological results both have an impact on the prognosis of oral squamous cell carcinoma in patients who have undergone neck dissection

BackgroundLocoregional surgical pathology, with surgical margins at the primary site and lymph node (LN) metastasis, particularly extranodal extension (ENE), plays an important role in the prognosis of oral squamous cell carcinoma (OSCC). In addition, systemic inflammatory response and nutritional status are associated with poor prognosis. PurposeThis study aimed to comprehensively assess the effect of inflammatory markers and locoregional factors on the prognosis of patients with OSCC who underwent neck dissection (ND). MethodsThis retrospective cohort study included patients who had undergone ND for OSCC between 2013 and 2021. The primary predictive variables were the weighted lymph node ratio (WLNR) and inflammatory markers. Primary outcome variables were overall survival (OS) and disease-free survival (DFS). ResultsAmong 153 patients (99 males, 54 females), 55 (35.9 %) had LN metastasis and 11 (7.2 %) exhibited ENE. The inflammatory markers lymphocyte/monocyte ratio (LMR), monocyte/albumin ratio (MAR), C-reactive protein/albumin ratio (CAR), and WLNR demonstrated significant cut-off values for survival, with values of 4.805, 104.72, 0.041, and 0.0235, respectively. The Cox proportional hazards model revealed significant differences in age, WLNR, LMR, MAR, CAR, and vascular, lymphatic, and perineural invasion (Pn). Multivariate analysis indicated that the hazard ratios (95 % confidence intervals) for WLNR (3.416; 1.542–7.566), MAR (2.404; 1.254–4.607), and Pn (2.516; 1.291–4.905) were independent variables for OS. ConclusionsIn patients with OSCC who underwent ND, the inflammatory marker MAR and locoregional factors WLNR and Pn were simultaneously identified as prognostic factors.

Evaluating Treatment Patterns and the Role of Neoadjuvant Chemotherapy in Plasmacytoid Urothelial Carcinoma: Insights from a Combined National and Institutional Series.

Plasmacytoid urothelial carcinoma (PUC) is a rare histologic subtype of urothelial carcinoma of the bladder (BC). Our objective was to characterize treatment patterns and outcomes of PUC in the NCDB and our recent institutional experience. The NCDB was queried for localized PUC cases between 2004 and 2020. Patients with PUC from a single institution (Yale School of Medicine) were also incorporated from 2021 onwards to not double-count patients. The primary outcomes were overall survival and treatment trends. A total of 146 patients were included, 123 from NCDB and 23 from Yale. The median overall survival (mOS) was 28 [IQR 7.5, 50.3] months, 23 [IQR 8.4, 46.3] months for the NCDB patients, and 36 [IQR 4.3, 68.1] for the Yale patients. The mOS for patients receiving neoadjuvant chemotherapy (NAC) was 60.0 [28.0, 91.9] vs. 14.8 months [0, 34.3] for patients without NAC, p = 0.038, though the benefit was not preserved in a Cox proportional hazard analysis incorporating the clinical stage, receipt of NAC, and age. The peritoneum was the most common site of metastasis (78.3%), followed by the liver and bones. Our findings underscore the formidable challenge posed by PUC, emphasizing its limited response to current therapies. Despite higher pT0 rates with NAC, the OS benefit remains inconclusive, highlighting the need for more effective treatments.

Evolution of the Neck Dissection

Cervical lymph nodes are the most common site of metastasis from head and neck cancer1 and are the single most important prognostic factor in treating head and neck cancer.2,3 Neck dissection is the standard treatment for clinical and occult metastasis of head and neck cancer to the cervical nodal basins.2 This review will discuss the evolution of neck dissection over the past two centuries, highlighting the surgeons and articles credited with the major advancements of the procedure.

Impact of diabetes mellitus and hypertension on renal function during first-line targeted therapy for metastatic renal cell carcinoma: a retrospective multicenter study.

Renal function deterioration during systemic therapy in patients with metastatic renal cell carcinoma (mRCC) is a long-term concern in treatment planning. Although hypertension (HTN) and diabetes mellitus (DM) are the most common factors that affect chronic kidney disease (CKD) development and progression, their impact on renal function during targeted therapy is unclear. This study investigated whether DM and HTN were associated with a decline in renal function during first-line targeted therapy for mRCC. This retrospective multicenter study analyzed patients receiving first-line targeted therapy for mRCC. They were classified as follows: group 1: HTN-, DM-; group 2: HTN+, DM-; group 3: HTN-, DM+; and group 4: HTN+, DM+. Changes in renal function and factors affecting progression to stage 4 CKD after targeted therapy were analyzed. Among the 424 enrolled patients, 303 (71.5%) and 121 (28.5%) were treated with sunitinib and pazopanib, respectively [median duration: 10.3 months, interquartile range (IQR), 3.1-37.0 months]. Although all groups showed a decreased mean estimated glomerular filtration rate (eGFR) after treatment (P<0.001 for group 1, group 2, and group 4, P=0.02 for group 3, respectively), there were no significant differences in changes in eGFR (∆eGFR) between groups (P=0.10). However, actual renal function change calculated using percent ∆eGFR (%∆eGFR) showed differences between groups (P=0.02); the %∆eGFR of group 4 was significantly lower compared with group 1 (P=0.008). The mean progression time to stage 4 CKD in group 4 (38.6 months) was significantly shorter compared to the other groups (P<0.001). Multivariate analysis identified increased age (P=0.008), increased number of metastatic sites (P=0.047), and DM and HTN coexistence (P<0.001) as predictors of progression to stage 4 CKD. Patients with DM and HTN experienced further decline in renal function and had a higher risk of progression to stage 4 CKD after targeted therapy compared to patients without these risk factors. Recognition and proactive management of DM and HTN are necessary to facilitate the proper administration of life-prolonging oncological treatments.

Therapeutic Insights into Low-intensity Vibration for Generating Induced Tumor-Suppressive Cells and Modulating the Bone Microenvironment

Bone frequently serves as a metastatic site for breast and prostate cancers. Given the potential of low-intensity vibration (LIV) to increase bone health and reduce cancer risk, this study investigated the impact of LIV on cancer cells, as well as noncancer cells such as lymphocytes and peripheral blood mononuclear cells (PBMCs). The results revealed that LIV exposure not only suppressed cancer cell migration but also triggered the generation of induced tumor-suppressing (iTS) cells. Conditioned medium (CM) derived from LIV-treated PBMCs shrank freshly isolated breast and prostate cancer tissues, and when CM was combined with a chemotherapeutic agent, additional antitumor effects were observed. Notably, iTS cell-derived CM hindered the maturation of the receptor activator of nuclear factor-kappa B ligand (RANKL)-stimulated bone-resorbing osteoclasts while promoting the differentiation of bone-forming osteoblasts. Intriguingly, the anticancer effects induced by LIV were replicated by simply shaking a cell-containing tube with a regular tube shaker. Using mass spectrometry-based proteomics, this study revealed enrichment of tumor-suppressing proteins, including enolase 1, moesin (MSN), and aldolase A (ALDOA), which are commonly found in oncogene-activated iTS cells, in LIV-induced CM. Sad1 and UNC-84 domain containing 1 (SUN1), a core component of the linker of the nucleoskeleton and cytoskeleton (LINC) complex, exhibited heightened expression, notably enhancing the response of lymphocytes to LIV. An ex vivo bone cancer model further demonstrated the potent anticancer effects of lymphocyte-derived CM. In conclusion, this study underscores the pivotal role of LIV in preventing bone loss in the tumor microenvironment.

Inpatient palliative care in metastatic adrenocortical carcinoma: a retrospective analysis using the National Inpatient Sample database.

The use of inpatient palliative care (IPC) in advanced cancer patients represents a well-established guideline recommendation. This study examines the utilization rates and patterns of IPC among patients with metastatic adrenocortical carcinoma (mACC). Relying on the Nationwide Inpatient Sample database (2007-2019), we tabulated IPC rates in mACC patients. Estimated annual percentage changes (EAPC) analyses as well as multivariable logistic regression models (MLRM) predicting IPC use were fitted. Of 2040 mACC patients, 238 (12%) received IPC. Overall, the rate of IPC increased from 3.7% to 19.1% between 2007 and 2019 (EAPC +9.6%, P=0.001). During the same period, in-hospital mortality remained unchanged from 12.1 to 13.8% (EAPC 0.1%; P=0.97). Younger age at admission (<60 years; MLRM OR=0.70, P=0.013), solitary metastatic site (OR=0.63; P=0.015), and non-brain metastases (OR=0.62; P=0.033) were all associated with lower IPC use. In mACC patients, IPC use has increased from a marginal 3.7% to a moderate annual value of 19.1% in the most recent study year. These rates were not driven by a concomitant increase in in-hospital mortality (12.1% to 13.8%; P=0.9). and may be interpreted as an improvement in quality of care. Despite this encouraging increase, some patient characteristics herald lower IPC use. In consequence, younger patients, those with solitary metastatic sites, and non-brain metastases should be carefully considered for IPC to decrease or completely reduce the IPC access barrier maximally.

329. PREDICTION OF MEDIASTINAL LYMPH NODE METASTASIS IN SIEWERT TYPE I/II ESOPHAGOGASTRIC JUNCTION CANCER WITH ESOPHAGEAL INVASION

Abstract Background Mediastinal lymph node dissection (LND) is a critical factor to decide the surgical strategy for Esophagogastric junction (EGJ) cancers. As a result of a prospective multicenter study in Japan, surgical algorithm including the extent of LND for EGJ cancers has recently been proposed according to the length of esophageal invasion. However, preoperative measure predicting upper mediastinal LN metastasis is still lacking, and the oncologic efficacy of mediastinal LND remain unknown. Methods The aim of this study was to identify preoperative factors predicting mediastinal LN metastasis, and we hypothesized that preoperative CT image would be of utility. Patients who underwent surgical treatment for Siewert Type I/II EGJ cancer with esophageal invasion with curative intent between 2000 and 2022 at the Tokai University Hospital were retrospectively reviewed. Results A total of 103 patients were enrolled. Among them, 55, 74, and 74 patients underwent upper, middle, and lower mediastinal LND, respectively. Upper/middle/lower mediastinal LN metastasis was observed in 14/13/23 of those patients, respectively, with lower thoracic paraesophageal LNs (29%), middle thoracic paraesophageal LNs (18%), and right recurrent nerve LNs (16%) being the three most common metastatic sites. Estimated invasion depth of the primary lesion≧cT3 (p≦0.007), tumor size≧4cm (p≦0.002), esophageal invasion length≧4cm (p≦0.007) and minor axis of the LN≧5mm by preoperative CT image (p&amp;lt;0.001) were significant preoperative factors related to mediastinal LN metastasis. Conclusion Clinical T factor, tumor size, the size of mediastinal LN by CT image, as well as esophageal invasion length, were important preoperative factors to predict mediastinal LN metastasis, and those factors should be taken into consideration to decide the surgical strategy for EGJ cancers with esophageal invasion. Survival impact of mediastinal LND still remain unclear, and further accumulation of cases and prospective studies are awaited.

Development and validation of a diagnostic and prognostic model for bone metastasis of intrahepatic cholangiocarcinoma: a population-based analysis.

Bone metastasis (BM) is a common site of metastasis in patients with intrahepatic cholangiocarcinoma (ICC), significantly impacting the quality of life and prognosis of affected individuals. This investigation aimed to assess the risk of BM development in ICC patients and to prognosticate for patients with ICC-associated BM (ICCBM) through the construction of two nomograms. We conducted a retrospective analysis of data from 2,651 ICC patients, including 148 cases of BM, documented in the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. Independent predictors for the occurrence of BM in ICC patients were identified via univariate and multivariate logistic regression analyses; simultaneously, independent prognostic indicators for ICCBM patients were ascertained through univariate and multivariate Cox regression analyses. The utility of the nomograms was evaluated through calibration curves, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and Kaplan-Meier (KM) analysis. Independent risk factors for BM in ICC included sex, tumor size, lung metastasis, brain metastasis, and intrahepatic metastasis. For ICCBM patients, independent prognostic factors comprised age, chemotherapy, and radiotherapy. The prognostic nomogram exhibited C-indexes of 0.737 [95% confidential interval (CI): 0.682-0.792] for the training cohort and 0.696 (95% CI: 0.623-0.769) for the validation cohort. Calibration curves demonstrated strong concordance between predicted outcomes and observed events. The areas under the curve (AUC) for 3-, 6-, and 12-month cancer-specific survival (CSS) were 0.853, 0.781, and 0.739, respectively, in the training cohort, and 0.794, 0.822, and 0.780 in the validation cohort. DCA illustrated significant net benefits across a broad spectrum of threshold probabilities. KM analysis revealed 1-, 2-, and 3-year CSS rates of 23.91%, 7.55%, and 2.35%, respectively, with a median CSS of 6 months, underscoring the nomograms' capacity to distinctly stratify patients according to survival risk. The development of these nomograms offers substantial clinical utility in forecasting BM risk among ICC patients and prognosticating for those with ICCBM, thereby facilitating the formulation of more efficacious treatment modalities.

Multi-armored allogeneic MUC1 CAR T cells enhance efficacy and safety in triple-negative breast cancer.

Solid tumors, such as triple-negative breast cancer (TNBC), are biologically complex due to cellular heterogeneity, lack of tumor-specific antigens, and an immunosuppressive tumor microenvironment (TME). These challenges restrain chimeric antigen receptor (CAR) T cell efficacy, underlining the importance of armoring. In solid cancers, a localized tumor mass allows alternative administration routes, such as intratumoral delivery with the potential to improve efficacy and safety but may compromise metastatic-site treatment. Using a multi-layered CAR T cell engineering strategy that allowed a synergy between attributes, we show enhanced cytotoxic activity of MUC1 CAR T cells armored with PD1KO, tumor-specific interleukin-12 release, and TGFBR2KO attributes catered towards the TNBC TME. Intratumoral treatment effectively reduced distant tumors, suggesting retention of antigen-recognition benefits at metastatic sites. Overall, we provide preclinical evidence of armored non-alloreactive MUC1 CAR T cells greatly reducing high TNBC tumor burden in a TGFB1- and PD-L1-rich TME both at local and distant sites while preserving safety.

Practice patterns and predictors of treatment intensification in patients with metastatic castration-sensitive prostate cancer.

Treatment intensification beyond androgen deprivation therapy (ADT) has shown survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC). There is a need to better understand how these novel treatments fit in real-world practice. Using electronic medical records and administrative data, a population-based, retrospective cohort study of patients newly diagnosed with de novo mCSPC between 2010 and 2020 in Alberta, Canada, and initiated ADT was conducted. Treatment intensification was defined as the receipt of apalutamide, abiraterone acetate, enzalutamide, or chemotherapy (e.g., docetaxel) within 180 days of ADT initiation. A total of 2515 de novo mCSPC were identified, with 2098 (83%) patients initiating ADT post-diagnosis. Of those, 525 (25%) received intensification beyond ADT. The percentage of patients who were intensified was 3% in 2010-2013 and gradually increased to 67% in 2020. From 2014-2017, docetaxel was the most commonly used approach, although it was supplanted by abiraterone acetate, apalutamide and enzalutamide from 2018 onwards. In multivariable logistic regression analyses of patients diagnosed from 2014-2020, significant predictors of intensification were younger age at diagnosis, lower Charlson comorbidity index, greater number of metastatic sites, shorter time to ADT initiation, referral to a medical oncologist, transurethral resection of the prostate or radiation prior to ADT, and more recent year of diagnosis (all p<0.05). Intensification increased for patients living in rural areas and with higher disease burden in 2018+ compared to 2014-2017. There has been a considerable increase in the use of ADT intensification therapies that correspond with the timing of clinical trial data and approvals of novel agents.

Rare Metastasis of Cutaneous Leiomyosarcoma to the Inguinal Region: Case report and Literature review

Introduction: Cutaneous leiomyosarcoma (CLM) is a rare malignancy arising from smooth muscle cells in the skin. It constitutes 2%-3% of all cutaneous soft tissue sarcomas and is known for its propensity for local recurrence and distant metastasis. Common metastatic sites include the lungs, liver, and brain. Diagnosis involves clinical examination and histopathological analysis, while management typically involves surgical excision, with adjunctive therapies like radiation and chemotherapy often considered due to its aggressive nature. Metastasis rates are reported as 12% for dermal and 51% for subcutaneous CLM. Case Report: A 40-year-old female with a history of excised leiomyosarcoma on the right buttock presented with a large, painful mass in the right inguinal region. Imaging revealed a substantial subcutaneous mass with significant local invasion and inguinal lymphadenopathy. Histopathological examination confirmed metastatic leiomyosarcoma. The patient showed anemia and elevated white blood cell count. Literature Review: Various cases reveal that CLM typically presents as nodular masses, primarily managed by surgical excision. Metastasis is rare but can occur, particularly in subcutaneous tumors. Inguinal region metastasis is highly unusual, with most cases showing spread to distant organs or regional lymph nodes. Imaging and histopathological findings are crucial for diagnosis. Discussion: CLM, while less metastatic compared to other sarcomas, requires vigilant monitoring due to its potential for local recurrence and distant spread. Metastasis to the inguinal region is exceptionally rare, highlighting the need for ongoing research to better understand such anomalies. Conclusion: CLM generally has a better prognosis than other sarcomas, but early detection of recurrence and metastasis is crucial. The rare occurrence of inguinal region metastasis emphasizes the importance of comprehensive surveillance and further research to understand this phenomenon better.

Unveiling the Molecular Features of SCLC With a Clinical RNA Expression Panel

IntroductionThe translation of gene expression profiles of SCLC to clinical testing remains relatively unexplored. In this study, gene expression variations in SCLC were evaluated to identify potential biomarkers. MethodsRNA expression profiling was performed on 44 tumor samples from 35 patients diagnosed with SCLC using the clinically validated RNA Salah Targeted Expression Panel (RNA STEP). RNA sequencing (RNA-Seq) and immunohistochemistry were performed on two different SCLC cohorts, and correlation analyses were performed for the ASCL1, NEUROD1, POU2F3, and YAP1 genes and their corresponding proteins. RNA STEP and RNA-Seq results were evaluated for gene expression profiles and heterogeneity between SCLC primary and metastatic sites. RNA STEP gene expression profiles of independent SCLC samples (n = 35) were compared with lung adenocarcinoma (n = 160) and squamous cell carcinoma results (n = 25). ResultsThe RNA STEP results were highly correlated with RNA-Seq and immunohistochemistry results. The dominant transcription regulator by RNA STEP was ASCL1 in 74.2% of the samples, NEUROD1 in 20%, and POU2F3 in 2.9%. The ASCL1, NEUROD1, and POU2F3 gene expression profiles were heterogeneous between primary and metastatic sites. SCLCs displayed markedly high expression for targetable genes DLL3, EZH2, TERT, and RET. SCLCs were found to have relatively colder immune profiles than lung adenocarcinomas and squamous cell carcinomas, characterized by lower expression of HLA genes, immune cell, and immune checkpoint genes, except the LAG3 gene. ConclusionsClinical-grade SCLC RNA expression profiling has value for SCLC subtyping, design of clinical trials, and identification of patients for trials and potential targeted therapy.

Relationship between the combination of platelet count and neutrophil-lymphocyte ratio and prognosis of patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors plus chemotherapy: A retrospective cohort study.

The relationship between the combination of platelet count and neutrophil-lymphocyte ratio (COP-NLR) and prognosis in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitor (ICI) combination therapy with chemotherapy remains unclear. Thus, we investigated prognostic factors, including the COP-NLR, to identify patients who could benefit from the therapeutic efficacy of ICI combination therapy for advanced NSCLC. Furthermore, we evaluated the relationship between the COP-NLR score during ICI combination therapy and treatment response. We conducted a retrospective cohort study of 88 patients with NSCLC who initially received ICI combination therapy. The primary outcome was overall survival (OS). The prognostic factors were extracted using the Cox proportional hazards model. The relationship between COP-NLR score at 3 weeks after starting ICI combination therapy and a good response (complete response [CR] and partial response [PR]) to treatment was analyzed using the chi-square test. The median OS was 15.7 months. In the multivariable analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2, distant metastatic sites ≥2, and baseline COP-NLR scores of 1, 2 were extracted as significant poor prognostic factors. The proportion of patients with CR and PR in the 3-week COP-NLR score of 0 group was significantly higher than that in scores of 1, 2 group. Baseline COP-NLR, ECOG PS, and number of distant metastatic sites were prognostic factors in patients with NSCLC with ICI combination therapy. A lower 3-week COP-NLR was associated with a good response to treatment.

FDG PET/MRI in a Case of Isolated Abdominal Incisional Site Metastasis After Laparoscopic Surgery for Colon Cancer.

Abdominal-wall metastasis following laparoscopic surgery for colorectal cancer is rare. We describe FDG PET/MRI findings in a case of isolated abdominal incisional site metastasis after laparoscopic surgery for colon cancer. The abdominal-wall metastasis showed slight hyperintensity on T2-weighted fat-suppressed image and intense focal FDG uptake on PET. This case demonstrates the usefulness of FDG PET/MRI in detecting the atypical metastasis from colon cancer.

Optimizing the Outcome of Pediatric Metastatic Neuroblastoma in a Nontransplant Setting in a Developing Country: Retrospective Study from a Tertiary Cancer Center in India

Abstract Objective This article estimates the survival of children over 1 year of age diagnosed with metastatic neuroblastoma (NB) and treated in a nontransplant facility and determines the factors affecting survival. Materials and Method Case records of children aged 1 to 14 years treated for metastatic NB in our center from January 2008 to December 2017 were studied. Patients received conventional chemotherapy followed by surgery, radiotherapy, and metronomic maintenance chemotherapy. Results Eighty-nine patients with metastatic NB received treatment. Mean age was 3.5 years and male:female ratio was 1.1:1. The most common primary site was suprarenal (55%) and the most common site of metastasis was bone marrow (76%). Forty percent patients had multiple metastatic sites. Mean baseline lactate dehydrogenase (LDH) was 3724 U/L (range 303–16609 U/L) and 65% patients had LDH &gt; 750 U/L. Fifty-three patients (59.6%) had good response to chemotherapy as evidenced by clearance of metastatic disease, but out of them, 43 patients (81%) progressed subsequently. Twenty-six patients underwent surgery and 12 patients received maintenance therapy. Seventy-four patients (86%) developed recurrence and all but one died. Median time to recurrence and death were 9 months (range 0–120 months) and 10 months (range 1–123 months), respectively. At a median follow-up of 72 months (range 15–135 months), 16 patients are alive, with 5-year disease-free survival and overall survival of 17.6 and 18.4%, respectively. Age, baseline LDH, chemotherapy regimen, and response to treatment significantly affected survival. Conclusion Younger age, lower baseline LDH, and good response to chemotherapy appear to confer survival advantage in pediatric metastatic NB, and may be used for optimization of treatment in the nontransplant setting in developing countries.

Evaluating the Initial Experience and Clinical Impact of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) Scans in Prostate Cancer Management: A Retrospective Study in Iraq.

Background Prostate cancer is a significant health concern globally, especially in the Middle East, including Iraq. This study explores the adoption and impact of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) scans in Erbil, Iraq, from 2020 to 2023, marking a pivotal advancement in prostate cancer diagnostics in a region where the disease's prevalence is rising. Materials and methods Through a retrospective analysis at Medya Diagnostic Center in Erbil, Iraq, involving 172 patients, we assessed the feasibility, applicability, and clinical utility of PSMA PET/CT in the local population. Results The study highlights the modality's enhanced sensitivity and specificity in detecting prostate cancer and its metastases, with bone being the most frequent metastasis site. Despite positive outcomes, challenges such as integration into clinical practice, adherence to guidelines, and financial implications were identified. The majority of referrals came from medical oncologists, primarily for staging and response evaluation, indicating PSMA PET/CT's critical role in managing prostate cancer. The findings suggest a need for national guidelines, interdisciplinary collaboration, and educational initiatives to optimize the use of PSMA PET/CT in Iraq's healthcare setting. Conclusions This study contributes valuable insights into the early experiences with PSMA PET/CT, paving the way for improved prostate cancer diagnostics and management in similar contexts.

A rare case of adult rhabdomyosarcoma with adnexal metastasis responding tonon-conventional chemotherapy

Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma having a rare incidence among adults. It is a highly chemo-radiosensitivetumor among the pediatric population but has poor biology in adults with dismal outcomes. Due to the rarity of adult RMS, there areno well-defined treatment guidelines for adult RMS and are mostly managed with pediatric-defined protocols but lack similar response.Here, we present the case of an adult female with extremely atypical metastatic site RMS which showed an extraordinary response tonon-pediatric protocol, rather than adult sarcoma-based protocol. This might give an idea to have more research and trials in the futureto implement adult sarcoma-based therapy among adult RMS cases.

Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases.

Metastatic breast cancer is a devastating disease with very limited therapeutic options, calling for new therapeutic strategies. Oncogenic miRNAs have been shown to be associated with the metastatic potential of breast cancer and are implicated in tumor cell migration, invasion, and viability. However, it can be difficult to deliver an inhibitory RNA molecule to the tissue of interest. To overcome this challenge and deliver active antisense oligonucleotides to tumors, we utilized magnetic iron oxide nanoparticles as a delivery platform. These nanoparticles target tissues with increased vascular permeability, such as sites of inflammation or cancer. Delivery of these nanoparticles can be monitored in vivo by magnetic resonance imaging (MRI) due to their magnetic properties. Translation of this therapeutic approach into the clinic will be more accessible because of its compatibility with this relevant imaging modality. They can also be labeled with other imaging reporters such as a Cy5.5 near-infrared optical dye for correlative optical imaging and fluorescence microscopy. Here, we demonstrate that nanoparticles labeled with Cy5.5 and conjugated to therapeutic oligomers targeting oncogenic miRNA-10b (termed MN-anti-miR10b, or "nanodrug") administered intravenously accumulate in metastatic sites, opening a possibility for therapeutic intervention of metastatic breast cancer.

Proteomic insights into breast cancer response to brain cell-secreted factors

The most devastating feature of cancer cells is their ability to metastasize to distant sites in the body. HER2 + and TN breast cancers frequently metastasize to the brain and stay potentially dormant for years until favorable conditions support their proliferation. The sheltered and delicate nature of the brain prevents, however, early disease detection and effective delivery of therapeutic drugs. Moreover, the challenges associated with the acquisition of brain biopsies add compounding difficulties to exploring the mechanistic aspects of tumor development. To provide insights into the determinants of cancer cell behavior at the brain metastatic site, this study was aimed at exploring the early response of HER2 + breast cancer cells (SKBR3) to factors present in the brain perivascular niche. The neural microenvironment was simulated by using the secretome of a set of brain cells that come first in contact with the cancer cells upon crossing the blood brain barrier, i.e., endothelial cells, astrocytes, and microglia. Cytokine microarrays were used to investigate the secretome mediators of intercellular communication, and proteomic technologies for assessing the changes in the behavior of cancer cells upon exposure to the brain cell-secreted factors. The cytokines detected in the brain secretomes were supportive of inflammatory conditions, while the SKBR3 cells secreted numerous cancer-promoting growth factors that were either absent or present in lower abundance in the brain cell cultures, indicating that upon exposure the SKBR3 cells may have been deprived of favorable conditions for optimal growth. Altogether, the results suggest that the exposure of SKBR3 cells to the brain cell-secreted factors altered their growth potential and drove them toward a state of quiescence, with broader overall outcomes that affected cellular metabolism, adhesion and immune response processes. The findings of this study underscore the key role played by the neural niche in shaping the behavior of metastasized cancer cells, provide insights into the cellular cross-talk that may lead cancer cells into dormancy, and highlight novel opportunities for the development of metastatic breast cancer therapeutic strategies.

Leveraging PARP-1/2 to Target Distant Metastasis.

Poly (ADP-Ribose) Polymerase (PARP) inhibitors have changed the outcomes and therapeutic strategy for several cancer types. As a targeted therapeutic mainly for patients with BRCA1/2 mutations, PARP inhibitors have commonly been exploited for their capacity to prevent DNA repair. In this review, we discuss the multifaceted roles of PARP-1 and PARP-2 beyond DNA repair, including the impact of PARP-1 on chemokine signalling, immune modulation, and transcriptional regulation of gene expression, particularly in the contexts of angiogenesis and epithelial-to-mesenchymal transition (EMT). We evaluate the pre-clinical role of PARP inhibitors, either as single-agent or combination therapies, to block the metastatic process. Efficacy of PARP inhibitors was demonstrated via DNA repair-dependent and independent mechanisms, including DNA damage, cell migration, invasion, initial colonization at the metastatic site, osteoclastogenesis, and micrometastasis formation. Finally, we summarize the recent clinical advancements of PARP inhibitors in the prevention and progression of distant metastases, with a particular focus on specific metastatic sites and PARP-1 selective inhibitors. Overall, PARP inhibitors have demonstrated great potential in inhibiting the metastatic process, pointing the way for greater use in early cancer settings.