Chemoresistance is a major obstacle in triple negative breast cancer (TNBC), the most aggressive breast cancer subtype. Here we identify hypoxia-induced ECM re-modeler, lysyl oxidase (LOX) as a key ...inducer of chemoresistance by developing chemoresistant TNBC tumors in vivo and characterizing their transcriptomes by RNA-sequencing. Inhibiting LOX reduces collagen cross-linking and fibronectin assembly, increases drug penetration, and downregulates ITGA5/FN1 expression, resulting in inhibition of FAK/Src signaling, induction of apoptosis and re-sensitization to chemotherapy. Similarly, inhibiting FAK/Src results in chemosensitization. These effects are observed in 3D-cultured cell lines, tumor organoids, chemoresistant xenografts, syngeneic tumors and PDX models. Re-expressing the hypoxia-repressed miR-142-3p, which targets HIF1A, LOX and ITGA5, causes further suppression of the HIF-1α/LOX/ITGA5/FN1 axis. Notably, higher LOX, ITGA5, or FN1, or lower miR-142-3p levels are associated with shorter survival in chemotherapy-treated TNBC patients. These results provide strong pre-clinical rationale for developing and testing LOX inhibitors to overcome chemoresistance in TNBC patients.
Purpose
The HER2-low breast cancer is a newly recognized entity with the clinical characteristics is yet to be defined. We hypothesized that HER2-low breast cancer could lead to an increased rate of ...brain metastases in patients with localized breast cancer. We tested this hypothesis in a large cohort of breast cancer patients with long follow-up.
Methods
We included 2686 adult breast cancer patients followed up in Hacettepe University Cancer Center. Patients with 1 + positive HER2 expression and 2 + HER2 expression with a negative FISH were categorized as HER2-low disease. We evaluated the brain metastasis risk with binary logistic regression analyses and reported odds ratios (OR) with 95% confidence intervals (CI).
Results
During a median 95.4 (IQR 72.6–123.1) month follow-up, 184 patients developed brain metastasis (6.9%). The brain metastases were developed in 5.1% of the patients with HER2-negative disease, 8.5% of the patients with HER2-low disease, and 10.1% of the patients with HER2-positive disease. A multivariable binary logistic regression model demonstrated an increased risk of brain metastasis in patients with HER2-low disease (OR: 1.611, 95% CI 1.055–2.460,
p
= 0.027) and in HER2-positive patients (OR: 1.837, 95% CI 1.308–2.580,
p
< 0.001). Additionally, HR + -HER2-low disease was associated with a decreased DFS compared to HR + -HER2-negative disease (
p
= 0.008).
Conclusion
In this study, we observed an increased risk of brain metastasis in localized breast cancer patients with HER2-low disease. We think that a high level of vigilance and a low threshold for brain imaging could benefit HER2-low breast cancer patients similar to the patients with HER-positive disease.
In this study, a molecularly imprinted polymer film (P (ANI)@MIP) on the electrode surface was fabricated using aniline as a functional monomer and octreotide (OC) as a template molecule. The ...developed P (ANI)@MIP was electrochemically electropolymerized on a glassy carbon electrode (GCE) surface. Each step of MIP production was evaluated by viewing the Fe (CN)63-/4- signal obtained using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The P (ANI)@MIP film layer was studied with a scanning electron microscope (SEM), Raman, and contact angle measurements. The parameters consisting of monomer, template ratio, cycle number, removal solution, removal time, and rebinding time were optimized to obtain the best electrochemical sensor. The developed method was validated in line with ICH guidelines. The linear range, LOD, and LOQ were found as 10–80 fM, 0.801 fM, and 2.670 fM, respectively. The selectivity of the method was tested with the response of somatostatin and lanreotide from the same growth hormone family by comparing the OC response. The developed P (ANI)@MIP/GCE sensor is the first reported method for electrochemical analysis of OC. The P (ANI)@MIP/GCE sensor exhibited high sensitivity and selectivity for OC. The novel MIP sensor was used to determine OC in cancer patient plasma samples. The concentration of OC in cancer patients varied between 8.98 ng/mL and 10.10 ng/mL.
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•The first MIP study to determine ultra-trace anti-cancer Octreotide (OC) drug.•The P (ANI)@MIP/GCE sensor exhibited a linear between 10 fM-80 fM OC with LOD of 0.801 fM.•The validated P (ANI)@MIP/GCE sensor was applied to neuroendocrine cancer patients.
In this study, we aimed to assess clinicopathological factors affecting early and late recurrences in patients with operable breast cancer. Patients with early (≤5 years) and late (>5 years) ...recurrences were assessed. Prognostic factors for disease-free survival (DFS) were also evaluated in patients with recurrence. A total of 854 patients were included. There were 432 and 205 patients in the early and late recurrence groups, respectively. In multivariate analyses, HER2+ disease, lymph node metastasis, lymphovascular invasion (LVI), and high tumor grade were associated with increased risk of early recurrence, while HER2+ disease and LVI were associated with decreased risk of late recurrence. In multivariate analyses, presence of HER2+ disease and triple-negative breast cancer (TNBC) were poor prognostic factors for DFS in patients with early recurrence. Presence of LVI and perineural invasion (PNI) were poor prognostic factors for DFS in patients with late recurrence. Molecular subtypes and LVI were effective on the early and late recurrences. However, lymph node positivity and grade were only associated with the early recurrence. After 5 years, LVI and PNI were the prognostic factors for DFS.
Hepatocellular cancer (HCC) and biliary tract cancers (BTCs) have poor survival rates and a low likelihood of a cure, especially in advanced-stage disease. Early diagnosis is crucial and can ...significantly improve survival rates through curative treatment approaches. Current guidelines recommend abdominal ultrasonography (USG) and alpha-fetoprotein (AFP) monitoring for HCC screening in high-risk groups, and abdominal USG, magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) monitoring for biliary tract cancer. However, despite this screening strategy, many high-risk individuals still develop advanced-stage HCC and BTC. Blood-based biomarkers are being developed for use in HCC or BTC high-risk groups. Studies on AFP, AFP-L3, des-gamma-carboxy prothrombin, glypican-3 (GPC3), osteopontin (OPN), midkine (MK), neopterin, squamous cell carcinoma antigen (SCCA), Mac-2-binding protein (M2BP), cyclic guanosine monophosphate (cGMP), and interleukin-6 biomarkers for HCC screening have shown promising results when evaluated individually or in combination. In the case of BTCs, the potential applications of circulating tumor DNA, circulating microRNA, and circulating tumor cells in diagnosis are also promising. These biomarkers have shown potential in detecting BTCs in early stages, which can significantly improve patient outcomes. Additionally, these biomarkers hold promise for monitoring disease progression and evaluating response to therapy in BTC patients. However, further research is necessary to fully understand the clinical utility of these biomarkers in the diagnosis and management of HCC and BTCs.
Purpose
Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in cancer patients. However, the association of VTE with immunotherapy remains poorly defined. We therefore ...evaluated the frequency of VTE in patients receiving immunotherapy and tried to determine predisposing factors.
Methods
A total of 133 adult metastatic cancer patients treated with immunotherapy for any cancer between were included. Baseline demographics, ECOG performance status, type of tumors, and baseline blood count parameters were recorded. Possible predisposing factors were evaluated with univariate and multivariate analyses.
Results
The median age was 60 (interquartile range (IQR) 48–66) years, and the median follow-up was 10.1 (IQR 5.8–18.5) months. Renal cell carcinoma (26.3%) and melanoma (24.1%) were most common diagnoses. Fifteen patients (11.3%) had an episode of VTE. Most of the VTEs were diagnosed as pulmonary emboli (10/15; 67%). Eighty percent (12/15) of these VTE cases were detected incidentally. Patients with a baseline ECOG performance status of 1 or more (29.3% of patients) had a significantly increased risk of venous thrombosis (ECOG ≥1 vs. 0, HR: 3.023, 95% CI: 1.011–9.039,
p
=0.048). Other factors, including patient age, tumor type, body mass index, baseline thrombocyte, neutrophil, and lactate dehydrogenase levels were not significantly associated with VTE risk.
Conclusions
In this study, we observed VTE development in more than 10% of immunotherapy-treated patients and increased VTE risk in patients with poorer ECOG status. With the asymptomatic nature of VTEs in most cases, a high index of suspicion level for VTE is required in patients treated with immunotherapy.
We present demographic, clinical, laboratory characteristics and outcomes of the patients with solid malignancies and novel coronavirus disease (COVID‐19) collected from the National COVID‐19 ...Registry of Turkey. A total of 1523 patients with a current or past diagnosis of solid tumors and diagnosed with COVID‐19 (confirmed with PCR) between 11 March and 20 May 2020 were included. The primary outcome was 30‐day mortality. Median age was 61 (range: 18‐94), and 752 (49%) were male. The most common types of cancers were breast (19.8%), prostate (10.9%) and colorectal cancer (10.8%). 65% of the patients had at least one comorbidity. At least one COVID‐19‐directed therapy was given in 73% of the patients.. Hospitalization rate of the patients was 56.6% and intensive care unit admission rate was 11.4%. Seventy‐seven (5.1%) patients died within 30 days of diagnosis. The first multivariate model which included only the demographic and clinical characteristics showed older age, male gender and presence of diabetes and receipt of cytotoxic therapy to be associated with increased 30‐day mortality, while breast and prostate cancer diagnoses were associated with lower 30‐day mortality. In the second set, we further included laboratory parameters. The presence of leukocytosis (OR 6.7, 95% CI 3.3‐13.7, P < .001), lymphocytopenia (OR 3,1, 95% CI 1,6‐6,1, P = .001) and thrombocytopenia (OR 3,4 95% CI 1,5‐8,1, P = .005) were found to be associated with increased 30‐day mortality. Relatively lower mortality compared to Western countries and China mainly results from differences in baseline risk factors but may also implicate the importance of intensive supportive care.
What's new?
Patients with cancer represent a vulnerable population to COVID‐19 due to the immune‐suppressive effect of the treatment and disease itself, their older age, and the frequent presence of comorbid diseases. In this cohort analysis of 1523 patients with solid tumors diagnosed with COVID‐19, the 30‐day mortality rate was found to be 5.1%. Cancer type, older age, male gender, diabetes, and cytotoxic treatment within 4 weeks were significant clinical predictors of increased mortality. The relatively lower mortality compared with Western countries and China mainly results from differences in baseline risk factors, but may also implicate the importance of intensive supportive care.
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