Data_Sheet_1_The effectiveness and safety of acupuncture for chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.docx

ObjectivesThis systematic review and meta-analysis aimed to evaluate the effectiveness and safety of acupuncture on chemotherapy-induced peripheral neuropathy (CIPN).MethodsWe searched for relevant randomized controlled trials (RCTs) in PubMed, Cochrane Library, and Embase databases from their inception to 1 April 2022. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), Brief Pain Inventory-Short Form (BPI-SF), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), Numerical Rating Scale (NRS), and adverse events were the outcome measures. All studies had at least one of these outcome measures. Mean differences (MDs) with 95% confidence intervals (CIs) were assessed in the meta-analysis using the RevMan 5.3 software.ResultsFive studies were included in the analysis. The results showed that acupuncture and placebo acupuncture were not significantly different in reducing chemotherapy-induced neurotoxicity and functional disability (random-effects estimates; MD: 4.30; 95% CI: −0.85~9.45; P = 0.10; I2 = 74%). Acupuncture was better than placebo acupuncture in reducing pain severity and pain interference with patients' daily function (fixed-effect estimates; MD: −1.14; 95% CI: 1.87 to −0.42; P = 0.002; I2 = 13%). Acupuncture was not significantly different from placebo acupuncture in relieving CIPN symptoms (MD: −0.81; 95% CI: −2.02 to 0.40, P = 0.19). Acupuncture improved quality of life better than placebo acupuncture (MD: 10.10; 95% CI: 12.34 to 17.86, P = 0.01). No severe adverse events were recorded in all five studies.ConclusionThis meta-analysis suggests that acupuncture may be more effective and safer in reducing pain severity and pain interference with patients' daily function than placebo acupuncture. Additionally, acupuncture may improve the quality of life of patients with CIPN. However, large sample size studies are needed to confirm this conclusion.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324930, identifier: CRD42022324930.</p

SPECT/CT images of MDA-MB-231 and A549 tumors by targeting MT1-MMP.

<p>(A) Static planar images of MDA-MB-231 tumor-bearing mice model and A549 tumor-bearing mice model after administration of 11.1 MBq/kg of [^99mTc](HYNIC-AF7P)(tricine)(TPPTS) at 0.5 and 2 h post injection. Excess amount (200 μg) of free AF7P was injected for blocking test. (B) Quantification of [^99mTc](HYNIC-AF7P)(tricine)(TPPTS) and [^99mTc](HYNIC-AF7P)(tricine)(TPPTS) (Blocking) in MDA-MB-231 tumor-bearing mice. Quantification of [^99mTc](HYNIC-AF7P)(tricine)(TPPTS) in A549 tumor-bearing mice. ROIs are shown as mean %ID/g ± SD.</p

Development of a Radiolabeled Peptide-Based Probe Targeting MT1-MMP for Breast Cancer Detection

<div><p>Breast cancer is one of the most frequent and aggressive primary tumors among women of all races. Matrix metalloproteinase (MMPs), a family of zinc- and calcium-dependent secreted or membrane anchored endopeptidases, is overexpressed in varieties of diseases including breast cancer. Therefore, noninvasive visualization and quantification of MMP <i>in vivo</i> are of great interest in basic research and clinical application for breast cancer early diagnosis. Herein, we developed a ^99mTc labeled membrane type I matrix metalloproteinase (MT1-MMP) specific binding peptide, [^99mTc]-(HYNIC-AF7p)(tricine)(TPPTS), for <i>in vivo</i> detection of MDA-MB-231 breast tumor by single photon emission computed tomography (SPECT). [^99mTc]-(HYNIC-AF7p)(tricine)(TPPTS) demonstrated nice biostability and high MT1-MMP binding affinity <i>in vitro</i> and <i>in vivo</i>. Tumor-to-muscle ratio was found to reach to the highest (4.17±0.49) at 2 hour after intravenously administration of [^99mTc]-(HYNIC-AF7P)(tricine)(TPPTS) into MDA-MB-231 tumor bearing mice. Overall, [^99mTc]-(HYNIC-AF7P)(tricine)(TPPTS) demonstrated great potential for MT1-MMP targeted detection <i>in vivo</i> and it would be a promising molecular imaging probe that are probably beneficial to breast cancer early diagnoses.</p></div

Characterizations.

<p>(A) Chemical structure of [^99mTc]-(HYNIC-AF7p)(tricine)(TPPTS). (B) Radio-HPLC purity of [^99mTc]-(HYNIC-AF7p)(tricine)(TPPTS).</p

Cytotoxicity of AF7p analogs on MDA-MB-231 cells.

<p>No cytotoxicity was observed at different concentrations of AF7p, Cy5.5-AF7p and (HYNIC-AF7P)(tricine)(TPPTS).</p

Fluorescent immunohistochemistry for MT1-MMP expression in MDA-MB-435 and A549 tumors.

<p>More MT1-MMP expressed in MDA-MB-435 tumor was observed than that of in A549 tumor. Green: FITC conjugated donkey anti-Rabbit secondary antibody. Blue: DAPI. All signals were adjusted to the same scale. Scale bar equals10 μm.</p

Solution stability data for [^99mTc(HYNIC-AF7P)(tricine)(TPPTS)] in saline (A) and in the presence of excess cysteine (B) (1 mg/mL, pH = 7.4).

<p>Solution stability data for [^99mTc(HYNIC-AF7P)(tricine)(TPPTS)] in saline (A) and in the presence of excess cysteine (B) (1 mg/mL, pH = 7.4).</p

Biodistribution of [^99mTc]-(HYNIC-AF7p)(tricine)(TPPTS) in mice bearing MDA-MB-231 tumor.

<p>Biodistribution of [^99mTc]-(HYNIC-AF7p)(tricine)(TPPTS) in mice bearing MDA-MB-231 tumor.</p

Cell labeling.

<p>(A) Chemical structure of Cy5.5 AF7p. (B) Colocalization of Cy5.5-AF7p and MT1-MMP on MDA-MB-231 and A549 cells. Red color is from Cy5.5 for Cy5.5-AF7p distribution on cellular membrane. Green color is from FITC conjugated donkey anti-rabbit secondary antibody for MT1-MMP localization. Blue color is from DAPI for nuclei visualization. Yellow color is merged color from Red and Green, indicating the colocalization of Cy5.5-AF7p and MT1-MMP. Scale bar equals 10 μm. (C). Blocking test for the specificity of Cy5.5-AF7p to MT1-MMP. Little of Cy5.5-AF7p was able to label MT1-MMP after excess amount of AF7p blocking.</p

Tumor to organ ratios of [^99mTc]-(HYNIC-AF7p)(tricine)(TPPTS) in B mice bearing MDA-MB-231 tumor.

<p>Tumor to organ ratios of [^99mTc]-(HYNIC-AF7p)(tricine)(TPPTS) in B mice bearing MDA-MB-231 tumor.</p