PVA Electrospun Fibers Coated with PPy Nanoparticles for Wearable Strain Sensors.

Current conductive polymers win wide applications in smart strain-stress sensors, bioinspired actuators, and wearable electronics. This work investigates a novel strain sensor by using conductive polypyrrole (PPy) nanoparticles coated polyvinyl alcohol (PVA) fibers as matrix. The flexible, water-resistant PVA fibers are initially prepared by combined electrospinning and annealing techniques, and then are coated with PPy nanoparticles through in situ polymerization. The resultant PPy@PVA fibers exhibit stable, favorable electrical conductivities due to the uniform point-to-point connections among PPy nanoparticles, e.g. after three-time' polymerizations, the PPy@PVA3 fiber film presents a sheet resistance of ≈840 Ω sq-1 and a bulk conductivity of ≈32.1 mS cm-1 . Cyclic sensing tests reveal that, PPy@PVA sensors show linear relationships between the relative resistance variations and the applied strains, e.g. the linear deviation of PPy@PVA3 is only 0.9 % within 33 % strain. After long-term stretching/releasing cycles, the PPy@PVA sensor exhibits stable, durable, and reversible sensing behaviors, no evident "drift" is observed over 1,000 cycles (5,000 seconds).

The prevalence and genetic disorders spectrum of thalassemia among breast cancer patients in Jiangxi province, China.

Background: Thalassemia is a common inherited hematological disease with genetic disorders characterized by imbalanced synthesis of the globin chains. Due to the improvement of treatment methods, patients with thalassemia can survive for a long time. Therefore, it is not uncommon for patients with thalassemia suffering from malignant tumors. However, there are quite few reports on thalassemia patients complicated with breast cancer. Herein, we try to investigate the prevalence and genetic disorders spectrum of thalassemia in patients with breast cancer. Methods: Blood routing tests and serum ferritin analysis were conducted in 1887 breast cancer patients treated in the department of radiation oncology during 1 April 2020 and 30 March 2022. The suspected thalassemia carriers with small mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MCH) or mean corpuscular hemoglobin concentration (MCHC) but the concentration of serum ferritin within normal limits were further investigated by polymerase chain reaction (PCR) and flow through hybridization gene chip to detect common mutations of α-globin and ß-globin genes using Thalassemia Geno Array Diagnostic Kit. The prevalence and genetic mutation spectrum of thalassemia among breast cancer patients were analyzed. Results: Four hundred and eighty-nine suspected thalassemia carriers were detected by complete blood cell counts and serum ferritin analysis among 1887 breast cancer patients. One hundred and seven cases (5.7%) were identified as carriers of thalassemia, of which 55 cases (51.4%) were α-thalassemia, 50 cases (46.7%) were ß-thalassemia, and 2 cases (1.9%) were co-inheritance of α-thalassemia and ß-thalassemia simultaneously. In α-thalassemia, the most prevalent genotype is -SEA/αα; as for ß-thalassemia, ßIVS-II-654/ß is the most common genotype. The degree of anemia is more severe in ß-thalassemia than in α-thalassemia. Conclusion: This is the first comprehensive molecular epidemiological investigation on thalassemia among breast cancer patients. Our data indicated that thalassemia was not uncommon in breast cancer patients. The physicians should have the knowledge to avoid misdiagnosis as iron deficiency anemia.

Recent Advances in Chitosan and its Derivatives in Cancer Treatment.

Cancer has become a main public health issue globally. The conventional treatment measures for cancer include surgery, radiotherapy and chemotherapy. Among the various available treatment measures, chemotherapy is still one of the most important treatments for most cancer patients. However, chemotherapy for most cancers still faces many problems associated with a lot of adverse effects, which limit its therapeutic potency, low survival quality and discount cancer prognosis. In order to decrease these side effects and improve treatment effectiveness and patient's compliance, more targeted treatments are needed. Sustainable and controlled deliveries of drugs with controllable toxicities are expected to address these hurdles. Chitosan is the second most abundant natural polysaccharide, which has excellent biocompatibility and notable antitumor activity. Its biodegradability, biocompatibility, biodistribution, nontoxicity and immunogenicity free have made chitosan become a widely used polymer in the pharmacology, especially in oncotherapy. Here, we make a brief review of the main achievements in chitosan and its derivatives in pharmacology with a special focus on their agents delivery applications, immunomodulation, signal pathway modulation and antitumor activity to highlight their role in cancer treatment. Despite a large number of successful studies, the commercialization of chitosan copolymers is still a big challenge. The further development of polymerization technology may satisfy the unmet medical needs.

Fulvestrant May Falsely Increase 17ß-Estradiol Levels in Immunoassays: A Case Report of a 57-Year-Old Postmenopausal Patient With Recurrent Estrogen Receptor-Positive Breast Cancer.

The prognosis for female patients with locoregionally recurrent breast cancer has improved with the concurrent local and systemic treatment under multiple disciplinary teams. Radiotherapy is a valuable local treatment measure for unresectable locoregional recurrent breast cancer; however, reirradiation in previously irradiated areas is still a matter of debate. Antihormonal therapy achieves an overall survival benefit for most of these patients with estrogen receptor-positive (ER+) breast cancer in both adjuvant and metastatic settings. Fulvestrant is an ER antagonist and selective ER downregulator widely used in antihormonal therapy, especially in recurrent postmenopausal ER+ breast cancers. However, fulvestrant closely resembles 17ß-estradiol in its molecular structure which may result in false increases in serum 17ß-estradiol levels in commercially available immunoassays leading to incorrect medical decisions. Herein, we report a case of a 57-year-old postmenopausal patient with recurrent ER+ breast cancer treated with concurrent fulvestrant and reirradiation. There was a good clinical response, and the combination treatment was well tolerable. During the quarterly follow-up, we monitored a gradual increase of the serum 17ß-estradiol level in immunoassays, unexpectedly, because the patient underwent natural menopause 8 years ago. To rule out the suspected fulvestrant cross-reactivity with 17ß-estradiol in immunoassay, the patient's serum 17ß-estradiol levels were subsequently tested with the more sensitive and specific liquid chromatography-mass spectrometry (LC-MS) method, which confirmed 17ß-estradiol levels at the postmenopausal level. Concomitant fulvestrant with reirradiation seems to be a safe and effective therapy for locoregionally recurrent ER+ breast cancer. However, a falsely increased 17ß-estradiol may result from cross-reactivity between 17ß-estradiol and its molecular analog compounds, for example, fulvestrant. Therefore, it is important for the clinicians with the knowledge of this interaction to prevent unnecessary erroneous interpretation of results and avoid wrong medical decisions.

Immune Checkpoint Inhibitors Combined With Chemotherapy Compared With Chemotherapy Alone for Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: It is still controversial whether immune checkpoint inhibitors (ICIs) can improve the curative effect when added to original standard chemotherapy treatment for triple-negative breast cancer (TNBC). We compared their antitumor efficacy and adverse effects (AEs) to make a better clinical decision. METHODS: Seven databases were searched for eligible articles. Progression-free survival (PFS), overall survival (OS), and AEs were measured as the primary outcomes. RESULTS: Nine randomized controlled trials (RCTs) involving 4,501 patients were included. ICI+chemotherapy treatment achieved better PFS (hazard ratio [HR]: 0.78, [0.70-0.86], p < 0.00001), OS (HR: 0.86, [0.74-0.99], p = 0.04), and complete response (584/1,106 vs. 341/825, risk ratio [RR]: 1.38, [1.01-1.89], p = 0.04). With the prolongation of survival, the survival advantage of ICI+chemotherapy increased compared with chemotherapy. Subgroup analysis suggested that the addition of ICIs might not have a better effect in Asian patients, patients with locally advanced disease, or patients with brain metastases. In the toxicity analysis, more Grade 3-5 AEs and serious AEs were found in the ICI+chemotherapy group. For Grade 3-5 AEs, more cases of diarrhea, severe skin reactions, pneumonitis, hepatitis, and adrenal insufficiency were related to the ICI+chemotherapy group. CONCLUSIONS: ICI+chemotherapy appears to be better than chemotherapy alone for TNBC treatment, with better OS and PFS. However, its high rates of serious AEs need to be taken seriously. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registration: CRD42021276394.

Polysaccharides Derived from Saposhnikovia divaricata May Suppress Breast Cancer Through Activating Macrophages.

BACKGROUND: Saposhnikovia divaricata (SD) has been used in traditional Chinese medicine to treat pain, inflammation, and arthritis. Recently, it has been reported that SD extract may inhibit tumor growth, but the mechanism involved is elusive. The aim of this study was to investigate the anti-tumor activity of polysaccharides derived from SD in breast cancer and the underlying mechanisms. MATERIALS AND METHODS: Polysaccharides isolated from SD were analyzed using Fourier transform infrared (FT-IR) spectroscopy and gas chromatography-mass spectroscopy (GC-MS). Their effects on cell growth of U937, MCF-7, and MDA-MB-231, and tumor growth in a mouse MDA-MB 231 xenograft model were examined. Their role in U937 activation, MCF-7, and MDA-MB 231 cytokine release profiles were also tested. RESULTS: In vitro studies showed that SD polysaccharides (SDPs) promoted U937 cell growth dose-dependently, with no obvious effect on growth of breast cancer cell lines MCF-7 and MDA-MB-231. SDP also showed an antagonistic effect against the growth inhibition of U937 by the culture supernatants of MCF-7 and MDA-MB-231, and reversed the polarization status of U937. Treatment of SCID mice bearing MDA-MB-231-derived xenograft tumors with SDP significantly reduced tumor growth. At all tested concentrations, no obvious toxic side-effects were recorded. DISCUSSION: We tentatively concluded that SDPs potently promote the growth of U937 and activate it to inhibit the tumor growth of SCID mice bearing MDA-MB-231-derived xenograft tumors indirectly, with no obvious growth inhibition effects on MCF-7 and MDA-MB-231 in vitro. Our finding indicated that SDP could be a potential anticancer agent for breast cancer.

Concomitant fulvestrant with reirradiation for unresectable locoregional recurrent estrogen receptor positive (ER+) breast cancer: A case report and narrative review.

RATIONALE: Locoregional recurrence of breast cancer is a challenging issue for clinicians. Treatment options for unresectable recurrent estrogen receptor positive (ER+) breast cancer in previously irradiated area are limited. Some studies showed concomitant fulvestrant with radiation therapy might increase radiosensitivity compared with radiation alone in vitro, no in vivo reports yet. PATIENT CONCERN: Here, we present a case report and make a narrative review of concomitant fulvestrant with radiation therapy for unresectable locoregional recurrent ER+ breast cancer. The patient was treated with modified radical mastectomy in 2015, adjuvant chemotherapy, radiotherapy, followed by exemestane until November 2018, relapsed in internal mammary lymph nodes with sternum involved. DIAGNOSIS: The final diagnosis was breast cancer internal mammary lymph nodes metastasis with sternum involved. INTERVENTIONS: After diagnosis was made, concurrent fulvestrant with reirradiation as a palliative treatment were proposed under multiple disciplinary team. OUTCOMES: There was a good clinical response, enabling curative chance with radiation therapy to a total dose of 60 Gy. Computed tomography scan revealed no evidence of residual tumor. LESSONS: As far as we know, this is the first report concerning concomitant fulvestrant with reirradiation for unresectable locoregional recurrent ER+ breast cancer. Since no severe adverse events were observed, this strategy could be a suitable "loco-regional rescue therapy" to further reduce tumor progression or even reach a curative effect. Studies of this treatment strategy in randomized clinical trials are warranted to further assess its safety and effectiveness.

The incidence of postoperative radiotherapy-induced acute dermatitis in breast cancer and its influencing factors for Chinese women.

PURPOSE: To investigate the incidence of skin acute reaction and its influencing factors in postoperative breast cancer radiotherapy patients. METHODS: One hundred and seventy three cases of breast cancer patients treated with postoperative radiotherapy were consecutively enrolled from June 1, 2016 to July 31, 2017 in our breast cancer center. Irradiation technology includes conformal intensity-modulated radiotherapy and a conventional two-dimensional one with conventional fraction. Any acute radiation dermatitis was recorded and the influencing factors were analyzed at the end of the radiation treatment. RESULTS: Radiotherapy-induced acute dermatitis in patients with breast-conserving surgery was relatively mild. Among the 173 patients, 33 cases had no obvious changes in the skin (grade 0); 121 cases had grade 1 skin reactions, manifested as local dark erythema and dry peeling; 29 cases had grade 2 skin reactions, characterized by edema, hyperemia, or erosion part; no grade 3 cases of skin reactions were observed. The incidence of grade 0, grade 1, and grade 2 reactions in all patients was 19.1%, 69.9%, and 11.0%, respectively. The severity of skin acute reaction is independent of the tumor sites, molecular subtypes, patients' age, and irradiation modalities, but it depends on the surgical types, fields treated, and planned total radiation. There is a trend favoring no chemotherapy over chemotherapy, though p-value is 0.074. CONCLUSION: Skin acute reaction in postoperative radiotherapy breast cancer patients is generally common but mild, and there are quite a few patients who need interruption or cessation of the radiotherapy process. The patients need to be well informed and made aware that any skin reaction will likely be mild, especially for the breast-conserving patients.

CSF1 is involved in breast cancer progression through inducing monocyte differentiation and homing.

Despite the great progress in breast cancer research and treatment, measures for efficient targeting of triple­negative breast cancer (TNBC) are still lacking. The well­established dependency of cancer cells on their microenvironment suggests that targeting the tumor niche might form a novel therapeutic approach. We identified the tumor­associated macrophage (TAM) infiltration in breast cancer tissues by immunohistochemistry, and analyzed overall survival (OS). U937 co­cultures with MDA­MB­231, MDA­MB­468 and MCF­7, respectively, to simulate in vivo cellular interactions were assessed. In hormone­independent breast cancer cell conditioned media (CM), U937 differentiates into M2 macrophage as identified by morphological changes and expression of specific surface antigens CD163 and CD204. Moreover, MDA­MB­231 recruits U937, and colony­stimulating factor 1 (CSF1) level in MDA­MB­231 and MDA­MB­468 CM is much higher than that of MCF­7. Overexpression of CSF1 in MCF­7 fails to rebuild its aggressiveness both in vitro and in vivo since CSF1 was not found extracellularly, while genetic inhibition of CSF1 in MDA­MB­231 abrogates TAM infiltration and consequently reduces tumorigenesis in non­obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Using various strategies we demonstrate that CSF1­induced TAMs specifically support breast cancer progression. Importantly, our results may reveal the efficacy of using targeted therapy against tumor niche and indicate that CSF1 inhibition may limit some breast cancer progression.

The importance of tissue confirmation of metastatic disease in patients with breast cancer: lesson from a brain metastasis case.

BACKGROUND: The discrepancy of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) statuses in breast cancers has been reported. Available systemic therapy for patients with breast cancer is based on the molecular subtypes as identified by IHC and/or FISH. However, these biomarkers may change throughout tumor progression. CASE PRESENTATION: We report a relatively uncommon case of a 39-year-old Chinese woman with local advanced breast cancer (LABC) treated with 6 cycles of docetaxel, doxorubicin and cyclophosphamide (TAC) regimen neoadjuvant chemotherapy, and subsequently mastectomy, intensity-modulated radiation therapy (IMRT) and tamoxifen followed as regularly. Brain metastatic event appeared in 6 months after mastectomy. Treatment for brain metastasis was surgical resection and followed by whole brain radiotherapy (WBRT) approved by multidisciplinary team (MDT). Initial pathological diagnosis was IDC, cT4N1M0, luminal B (ER+ 90%, PR+90%, HER2 0, Ki67+ 70%) based on ultrasound-guided core needle biopsy. Surgical pathology revealed IDC, pT2N3M0 luminal B (ER+ 20%, PR+20%, HER2 0, Ki67+ 20%). Histological response to neoadjuvant chemotherapy is grade 3 according to the Miller/Payne grading system. Final pathology of brain metastasis showed a HER2 overexpression metastatic breast cancer luminal B (ER+ 70%, PR+ 70%, HER2 2+, Ki67+ 30%), FISH confirmed HER2 overexpression. Weekly paclitaxel plus trastuzumab was given for 12 weeks, then trastuzumab every 3 weeks for a whole year. Patient follow-up is still ongoing, no new events appear yet. CONCLUSIONS: The determination of hormone receptors and HER2 status should be routinely performed in all involved tissues, if possible, and systemic therapy should be tailored following the latest finding.

Tumor associated macrophage × cancer cell hybrids may acquire cancer stem cell properties in breast cancer.

Breast cancer is one of the most frequently diagnosed cancers among women, and metastasis makes it lethal. Tumor-associated macrophages (TAMs) that acquire an alternatively activated macrophage (M2) phenotype may promote metastasis. However, the underlying mechanisms are still elusive. Here, we examined how TAMs interact with breast cancer cells to promote metastasis. Immunohistochemistry was used to examine the expression of the M2-specific antigen CD163 in paraffin-embedded mammary carcinoma blocks to explore fusion events in breast cancer patients. U937 cells were used as a substitute for human monocytes, and these cells differentiated into M2 macrophages following phorbol 12-myristate 13-acetate (PMA) and M-CSF stimulation. M2 macrophages and the breast cancer cell lines MCF-7 and MDA-MB-231 fused in the presence of 50% polyethylene glycol. Hybrids were isolated by fluorescence-activated cell sorting, and the relevant cell biological properties were compared with their parental counterparts. Breast cancer stem cell (BCSC)-related markers were quantified by immunofluorescence staining, RT-PCR, quantitative RT-PCR and/or western blotting. The tumor-initiating and metastatic capacities of the hybrids and their parental counterparts were assessed in NOD/SCID mice. We found that the CD163 expression rate in breast cancer tissues varied significantly and correlated with estrogen receptor status (p<0.05). The fusion efficiency of either breast cancer cell line with M2 macrophages ranged from 1.81 to 6.47% in the presence of PEG, and no significant difference was observed between the breast cancer cell lines used (p>0.05). Characterization of the fusion hybrids revealed a more aggressive phenotype, including increased migration, invasion and tumorigenicity, but reduced proliferative ability, compared with the parental lines. The hybrids also gained a CD44(+)CD24(-/low) phenotype and over-expressed epithelial-mesenchymal transition-associated genes. These results indicate that TAMs may promote breast cancer metastasis through cell fusion, and the hybrids may gain a BCSC phenotype.

Prostaglandin E2 upregulates survivin expression via the EP1 receptor in hepatocellular carcinoma cells.

AIMS: Cyclooxygenase-2 (COX-2)-controlled production of prostaglandin E(2) (PGE(2)) has been implicated in cell growth and metastasis in many cancers. Recent studies have found that COX-2 is co-expressed with survivin in many cancers. Survivin is a member of the inhibitor-of-apoptosis protein family. Some COX-2 inhibitors (e.g., celecoxib) can reduce the expression of survivin. However, little is known about the mechanism of PGE(2)-mediated expression of survivin. This study was designed to uncover the effect of PGE(2) on survivin expression in hepatocellular carcinoma cells. MAIN METHODS: The effects of PGE(2) and EP1 agonist on survivin expression were examined in HUH-7 and HepG2 cells. Plasmid transfection and EP1 siRNA were used to regulate the expression of COX-2 and the EP1 receptor protein. KEY FINDINGS: PGE(2) treatment increased survivin expression 2.3-fold. COX-2 overexpression resulted in a similar level of survivin upregulation. However, this effect was suppressed by treatment with celecoxib. EP1 receptor transfection or treatment with a selective EP1 agonist mimicked the effect of PGE(2) treatment. Conversely, the PGE(2)-induced upregulation of survivin was blocked by treatment with a selective EP1 antagonist or siRNA against the EP1 receptor. The phosphorylation of EGFR and Akt were elevated in EP1 agonist-treated cells, and both EGFR and PI3K inhibitors suppressed the upregulation of survivin induced by PGE(2) or EP1 agonist. SIGNIFICANCE: PGE(2) regulates survivin expression in hepatocellular carcinoma cells through the EP1 receptor by activating the EGFR/PI3K pathway. Targeting the PGE(2)/EP1/survivin signaling pathway may aid the development of new therapeutic strategies for both the prevention and treatment of this cancer.