We undertook an early phase II study of mixed 19‐peptide cancer vaccine monotherapy for 14 advanced metastatic triple‐negative breast cancer (mTNBC) patients refractory to systemic chemotherapy to ...develop a new type of cancer vaccine. The treatment protocol consisted of a weekly vaccination for 6 weeks, and there were no severe adverse events related to the vaccination throughout the trial. Increase of peptide‐specific IgG against the vaccinated human leukocyte antigen‐matched peptides, but not against the nonmatched peptides, was positively correlated with overall survival (OS) (P < .01). The median OS was 11.5 or 24.4 months in all 14 patients or the 10 patients who completed the vaccination. The patients with lower C‐reactive protein levels or 3 or fewer systemic chemotherapies were favorable candidates for this treatment. Advancement of this therapy to the next stage of study could be warranted based on the safety and immune boosting determined herein (clinical trial registration number: UMIN000014616).
Immune boosting specific to the vaccinated human leukocyte antigen‐matched peptides at the cellular and humoral levels was observed in the vast majority of patients with refractory metastatic triple‐negative breast cancer, who completed all 6 vaccinations.
Purpose
To determine the reproducibility, accuracy, and quantitative values of the auto strain ratio system (ASRS)—a newly developed strain elastography-based program.
Materials and methods
First, ...the accuracy of ASRS was verified using a breast phantom. A prospective clinical study was then performed in patients. Two hundred and one women (mean age 52.4 years ± SD 14.5) with 232 breast lesions (177 benign and 55 malignant) were enrolled in this study. We assessed the correlation between ASRS and manual strain ratio (MSR), calculating the diagnostic performance to determine the cut-off. The area under the receiver operating characteristic curve (AUC) was calculated.
Results
ASRS was strongly correlated with the subtle differences in phantom stiffness (
R
= 0.87). In the clinical study, there was a significant correlation between MSR and ASRS with
R
= 0.79 (
P
< 0.001). ASRS (cut-off = 3.9) had a sensitivity of 81.8%, specificity of 88.7%, accuracy of 87.1%, positive predictive value of 69.2%, and negative predictive value of 94%. The AUC of ASRS was 0.89.
Conclusion
The findings from this study have demonstrated that it is possible to quantify strain elastography and control its accuracy. ASRS is expected to contribute to the standardization of breast elastography.
ABSTRACT Matrix-producing carcinoma (MPC) of the breast is relatively rare. We report on a case of MPC of the breast during lactation. A female in her 30s noticed a lump in the upper inner and outer ...quadrants of her left breast 9 months into her pregnancy. She came hospital at one month after delivery. Ultrasonography revealed a hypoechoic tumor with an unclear border region. An MRI revealed a breast tumor approximately 19 mm in size, with dynamic studies demonstrating early contrast and ring enhancement. A core needle biopsy was performed, resulting in an histopathological diagnosis of invasive carcinoma Estrogen receptor-, Progesterone receptor-, Human epidermal growth factor receptor 2(HER2)-; stage I, T1cN0M0. Breast-conserving surgery and a sentinel lymph node biopsy (SLNB) were performed. The SLNB was negative for cancer. Chemotherapy (FEC100, DTX75) and radiotherapy were performed as adjuvant therapies. Seventeen months after surgery, the patient is recurrence-free.
SUMMARY
The existence and formation of covalent lignin–carbohydrate (LC) linkages in plant cell walls has long been a matter of debate in terms of their roles in cell wall development and biomass ...use. Of the various putative LC linkages proposed to date, evidence of the native existence and formation mechanism of phenyl glycoside (PG)‐type LC linkages in planta is particularly scarce. The present study aimed to explore previously overlooked mechanisms for the formation of PG‐type LC linkages through the incorporation of monolignol glucosides, which are possible lignin precursors, into lignin polymers during lignification. Peroxidase‐catalyzed lignin polymerization of coniferyl alcohol in the presence of coniferin and syringin in vitro resulted in the generation of PG‐type LC linkages in synthetic lignin polymers, possibly via nucleophilic addition onto quinone methide (QM) intermediates formed during polymerization. Biomimetic lignin polymerization of coniferin via the β‐glucosidase/peroxidase system also resulted in the generation of PG‐type as well as alkyl glycoside‐type LC linkages. This occurred via non‐enzymatic QM‐involving reactions and also via enzymatic transglycosylations involving β‐glucosidase, which was demonstrated by in‐depth structural analysis of the synthetic lignins by two‐dimensional NMR. We collected heteronuclear single‐quantum coherence (HSQC) NMR for native cell wall fractions prepared from pine (Pinus taeda), eucalyptus (Eucalyptus camaldulensis), acacia (Acacia mangium), poplar (Populus × eurarnericana) and bamboo (Phyllostachys edulis) wood samples, which exhibited correlations, albeit at low levels, that were well matched with those of the PG‐type LC linkages in synthetic lignins incorporating monolignol glucosides. Overall, our results provide a molecular basis for feasible mechanisms for the generation of PG‐type LC linkages from monolignol glucosides and further substantiates their existence in planta.
Significance Statement
Biomimetic lignin polymerization with monolignol glucosides, which are possible lignin precursors, produces synthetic lignin polymers containing phenyl glycoside‐type lignin–carbohydrate linkages. Comparisons of NMR spectra of native cell wall fractions and synthetic lignins incorporating monolignol glucosides support the in planta occurrence of such LC linkages arising from monolignol glucosides.
ABSTRACT Numerous improvements and advances in operational methods and techniques have occurred in the area of reconstruction for esophageal cancer. Patients with thoracic esophageal cancer who have ...previously had a gastrectomy usually undergo reconstruction using the colon and small intestine. The incidence of organ necrosis is not necessarily low after reconstruction with those organs. Generally, the main types of skin flaps and musculocutaneous flaps used for cervical and other esophageal reconstructions are deltopectoral (DP) flaps, pedicled musculocutaneous latissimus dorsi flaps and free anteriolateral thigh flaps. This kind of reconstruction is low invasive, relatively simple, and also causes very few fatal post-operative complications. Therefore, it is considered to be an effective reconstruction choice for the following types of patients: poor risk patients, patients whose gastrointestinal (GI) tract cannot be used for their reconstruction for some reason, and patients having a second reconstruction due to complications caused by organ necrosis after their first GI tract reconstruction.
Abstract
Purpose: Our results from the previous clinical trials using personalized peptide vaccines (PPV) combined conventional chemo-hormonal therapies have confirmed the potential for clinical ...benefit in patients who had higher IgG antibody and/or CTL response to the immunized PPV (SABCS 2018 U Toh etc.). The aim of this study is to evaluate the association between the serum immunologic factors including cytokines, haptoglobin (HP), B-cell activating factor (BAFF) etc. and the clinical outcome of patients(pt) with metastatic breast cancer (mBC) who treated by personalized peptide vaccines (PPV). Methods: Peripheral blood samples from 57 pts and 52 pts obtained before and after the vaccination of PPV, respectively. Serum HP and IL-6 were analyzed by ELISA(R&D Systems, Life Technologies)and bead-based multiplex assays(Luminex 200 system)were performed for GM-CSF,IFN-γ,TNF-α, BAFF, TGF-β, IFNγ-induced protein 10(IP-10), IL-1β, IL-2,-4,-5,-8, -10. The association between each factor and clinical outcome was statistically evaluated. Results: Pt’s group (n=28) with low BAFF and high HP level (>544 pg/ml), high IFN-γ and high HP level or low IL-8 and high HP level before PPV treatment showed a significantly shorter median survival time (MST; p=0.015;0.068;0.002, respectively). There was no difference in high BAFF, low IFN-γ or high IL-8 level group(n=29). In contrast, pt’s group with low serum level of IL-10, GM-CSF, IL-5, IL-4 and low HP level (<544 pg/ml MV) after PPV treatment associated with significantly shorter MST (p=0.002; 0.001; 0.001; <0.001, respectively). Conclusions: The combination of serum levels of HP and BAFF, IFN-γ or cytokines of IL-8, -10, - 5, -4 might be useful prognostic biomarkers for mBC pts receiving PPV therapy.
Citation Format: Uhi Toh, Shuko Saku, Yuko Takao, Sayaka Sakurai, Miki Takenaka, Shigeki Shichijo, Kyogo Itoh, Yoshito Akagi. Analysis of serum immune biomarkers for response to therapeutic personalized peptide vaccination in patients with metastatic breast cancer abstract. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-21.
ABSTRACT Currently, breast conserving surgery has been adopted to treat more than half of all breast cancer patients in Japan. When performing breast-conserving surgery, an appropriate margin needs ...to be determined for radical cure. The resection volume influences the esthetic outcome, but a cancer-positive resection stump is also important risk factor of local recurrence. Additionally, the degree of cancer progression influences the surgical method, so understanding the appropriate resection margin is necessary for the surgeons. We report here on a 50-year old patient whose intra-ductal cancer progression was shown, as predicted, by contrast SMI (superb micro-vascular imaging). A one-cm size tumor mass was palpable with a clear boundary. B-mode ultrasound confirmed the presence of a breast duct towards the nipple from the tumor mass. Using contrast SMI, an accelerated blood flow was detected around the duct, which suggested intra-ductal progression. The pathological results also showed intra-ductal progression to the nipple from the tumor. Around the progression area, a meandering vessel was found and the vessel was able to be visualized by contrast SMI.
The present study assessed plasma IgG in patients with metastatic recurrent breast cancer (mrBC) that is reactive to various T-cell epitope peptides of prostate-related antigens (PRAs), such as ...prostate-specific antigen, prostate-specific membrane antigen and prostate acid phosphatase. Patients were treated with personalized peptide vaccines (PPVs) which were selected and administered from a panel of candidate peptides based on human leukocyte antigen-types and prevaccination IgG levels to each peptide. The peptide panel consisted of 27 cytotoxic T-lymphocyte-epitope peptides derived from tumor-associated antigens, not including PRA. PRA peptides and peptide panels were retrospectively analyzed in 77 PPV-treated patients. The results revealed that PRA reactive IgG levels were increased after vaccination in 31 of the 97 patients included in the present study. Although there was no significant association between anti-PRA peptide levels and progression-free survival (PFS) or overall survival, anti-PRA peptide levels were significantly associated with PFS (P=0.009) in estrogen-receptor positive (ER+) patients with cancer. The results suggested that plasma anti-PRA IgG levels may be a useful prognostic marker for monitoring PPVs, particularly for ER+ patients with mrBC (trial registration no. from the UMIN Clinical Trials Registry, UMIN000001844).
ABSTRACT Cholesterol crystal embolization (CCE) is a rare systemic embolism caused by formation of cholesterol crystals from atherosclerotic plaques. CCE usually occurs during vascular manipulation ...such as vascular surgery or endovascular catheter manipulation, or due to anticoagulation or thrombolytic therapy. We report a rare case of localized intestinal ulcer with active hemorrhage caused by spontaneous CCE. An 83-year-old man with a history of hypertension and diabetes was treated with a percutaneous coronary intervention (PCI) for myocardial infarction. Melena occurred eight days after PCI. An abdominal computed tomography revealed small intestinal ulcer, extravasation of the gastrointestinal tract and bleeding in the abdominal cavity. The patient was diagnosed as bleeding from the small intestinal ulcer, so an emergency laparotomy was performed. Partial resection of the small intestine was performed. A histopathological examination indicated that small intestine obstruction was caused by CCE. A histopathological examination indicated that small intestinal obstruction was caused by CCE. Therefore, in cases of intestinal obstruction after vascular manipulation, CCE should also be considered.
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