The cellular programs that mediate therapy resistance are often important drivers of metastasis, a phenomenon that needs to be understood better to improve screening and treatment options for cancer patients. Although this issue has been studied extensively for chemotherapy, less is known about a causal link between resistance to radiation therapy and metastasis. We investigated this problem in triple-negative breast cancer (TNBC) and established that radiation resistant tumor cells have enhanced metastatic capacity, especially to bone.
View Article and Find Full Text PDFAims: This project aimed to evaluate current practices of trained nurses performing implantable cardiac monitor (ICM) implantations and remote follow-ups in Italy, assessing hospital protocols and nurses' perceptions.
Methods: An anonymous survey was conducted among 163 trained nurses across 75 Italian hospitals, focusing on their ICM implantation and remote monitoring practices. Data collected included hospital characteristics and protocols, barriers to implementation, and nurses' feedback on their experiences.
Tumors lacking the BRCA1 and BRCA2 (BRCA) hereditary breast cancer genes display heightened sensitivity to anti-cancer treatments, such as inhibitors of poly (ADP-ribose) polymerase 1 (PARP1). However, when resistance develops, treatments are lacking. Using CRISPR technology, we discovered that enhancing homologous recombination through increased DNA end resection in BRCA1-deficient cells by loss of the 53BP1-Shieldin complex-which is associated with resistance to PARP inhibitors-also heightens sensitivity to DNA nicks.
View Article and Find Full Text PDFIntroduction: Among older adults with cancer receiving chemotherapy, frailty indices predict OS and toxicity. Given the increased use of immunotherapy and targeted therapy for advanced non-small cell lung cancer (aNSCLC), we evaluated frailty and Karnofsky Performance Status (KPS) among older adults with aNSCLC receiving chemotherapy, immunotherapy, and/or targeted therapy.
Methods: Patients aged ≥ 65 with aNSCLC starting systemic therapy with non-curative intent underwent geriatric assessments over 6 months.
Although programmed cell death ligand 1 (PD-L1) is best known for its role in immune suppression, tumor-intrinsic functions are emerging. Here, we report that tumor cells that express PD-L1 are sensitive to ferroptosis inducers such as imidazole ketone erastin (IKE). PD-L1 promotes ferroptosis sensitivity because it suppresses SLC7A11 expression and diminishes glutathione levels.
View Article and Find Full Text PDFThe high rate of recurrence after radiation therapy in triple-negative breast cancer (TNBC) indicates that novel approaches and targets are needed to enhance radiosensitivity. Here, we report that neuropilin-2 (NRP2), a receptor for vascular endothelial growth factor (VEGF) that is enriched on subpopulations of TNBC cells with stem cell properties, is an effective therapeutic target for sensitizing TNBC to radiotherapy. Specifically, VEGF/NRP2 signaling induces nitric oxide synthase 2 (NOS2) transcription by a mechanism dependent on Gli1.
View Article and Find Full Text PDFTo evaluate if a preoperative medical treatment with the GnRH-antagonist relugolix in combination therapy in a series of patients with abnormal uterine bleeding associated with uterine myomas may correct the anemia before scheduled surgery for myoma-associated AUB. Thirty-one patients scheduled for surgery underwent a pre-operative three-month course with a daily oral tablet of 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethindrone acetate.
View Article and Find Full Text PDFBackground: Shoulder instability in pediatric and adolescent patients can be treated operatively via arthroscopic or open procedures, but there a paucity of evidence to support the incidence of these treatment modalities over time. It is hypothesized that the overall rate of arthroscopic shoulder stabilization procedures will increase over time. Given advances in open stabilization techniques, we also hypothesized that the rate of open procedures may be increasing.
View Article and Find Full Text PDFUnlabelled: Patients with castration-resistant prostate cancer (CRPC) are generally unresponsive to tumor targeted and immunotherapies. Whether genetic alterations acquired during the evolution of CRPC impact immune and immunotherapy responses is largely unknown. Using our innovative electroporation-based mouse models, we generated distinct genetic subtypes of CRPC found in patients and uncovered unique immune microenvironments.
View Article and Find Full Text PDFThis case study presents a 66-year-old man referred to the Otolaryngology and Head and Neck Surgery department due to a one-history of persistent pain in the left posterior cervical region. No abnormalities were detected in the oral and pharyngeal regions during clinical and endoscopic examinations. Subsequently, a magnetic resonance imaging revealed a lesion (14 × 12 × 14 mm) into the left parapharyngeal space, with high signal intensity on T2-weighted images, enhancement after contrast medium, restricted signal on diffusion weighted imaging and high vascularization on perfusion MRI.
View Article and Find Full Text PDFPurpose: Patients from diverse racial, ethnic, and socio-economic backgrounds may be particularly vulnerable to experiencing undue social and financial burdens ("collateral damage") from a metastatic breast cancer (mBC) diagnosis; however, these challenges have not been well explored in diverse populations.
Methods: From May 2022 to May 2023, English- or Spanish-speaking adults with mBC treated at four New York-Presbyterian (NYP) sites were invited to complete a survey that assessed collateral damage, social determinants of health, physical and psychosocial well-being, and patient-provider communication. Fisher's exact and the Kruskal-Wallis rank-sum tests assessed differences by race and ethnicity.
We are interested in the contribution of integrins and the extracellular matrix to epithelial differentiation in carcinomas. This study was motivated by our finding that the Hippo effectors YAP and TAZ can sustain the expression of laminin 332 (LM332), the predominant ECM ligand for the integrin β4, in breast carcinoma cells with epithelial differentiation. More specifically, we observed that YAP and TAZ regulate the transcription of the LAMC2 subunit of LM332.
View Article and Find Full Text PDFPurpose: A metastatic breast cancer (mBC) diagnosis can affect physical and emotional well-being. However, racial and ethnic differences in receipt of outpatient psychosocial care and supportive care medications in adults with mBC are not well described.
Methods: Adults with mBC were identified in the INSIGHT-Clinical Research Network, a database inclusive of >12 million patients receiving care across six New York City health systems.
Background: Preoperative risk factors contributing to poor outcomes after arthroscopic partial meniscectomy (APM) have not yet been consolidated and codified into an index scoring system used to predict APM success.
Purpose: To create an index score using available preoperative factors to predict the likelihood of favorable postoperative outcomes after APM.
Study Design: Case-control study; Level of evidence, 3.
Purpose: To evaluate the efficacy and long-term safety (up to 108 months) of treatment with Dienogest in patients with endometriosis.
Methods: Patients with chronic pelvic pain endometriosis-related were enrolled in this observational study from June 2012 to July 2021. The patients enrolled took Dienogest 2 mg as a single daily administration.
Understanding the cell biological mechanisms that enable tumor cells to persist after therapy is necessary to improve the treatment of recurrent disease. Here, we demonstrate that transient receptor potential channel 6 (TRPC6), a channel that mediates calcium entry, contributes to the properties of breast cancer stem cells, including resistance to chemotherapy, and that tumor cells that persist after therapy are dependent on TRPC6. The mechanism involves the ability of TRPC6 to regulate integrin α6 mRNA splicing.
View Article and Find Full Text PDFIdentifying metabolic steps that are specifically required for the survival of cancer cells but are dispensable in normal cells remains a challenge. Here we report a therapeutic vulnerability in a sugar nucleotide biosynthetic pathway that can be exploited in cancer cells with only a limited impact on normal cells. A systematic examination of conditionally essential metabolic enzymes revealed that UXS1, a Golgi enzyme that converts one sugar nucleotide (UDP-glucuronic acid, UDPGA) to another (UDP-xylose), is essential only in cells that express high levels of the enzyme immediately upstream of it, UGDH.
View Article and Find Full Text PDFImportance: O6-methylguanine-DNA methyltransferase (MGMT [OMIM 156569]) promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy for glioblastomas and is routinely used to guide treatment decisions. However, the utility of MGMT promoter status for low-grade and anaplastic gliomas remains unclear due to molecular heterogeneity and the lack of sufficiently large data sets.
Objective: To evaluate the association of mMGMT for low-grade and anaplastic gliomas with chemotherapy response.
In the first billion years after the Big Bang, sources of ultraviolet (UV) photons are believed to have ionized intergalactic hydrogen, rendering the Universe transparent to UV radiation. Galaxies brighter than the characteristic luminosity L* (refs. ) do not provide enough ionizing photons to drive this cosmic reionization.
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