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Τρίτη 13 Ιουλίου 2021

Plasma level of prostate related-antigen peptide-reactive IgG is a prognostic factor of patients with breast cancer treated with personalized peptide vaccines

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Exp Ther Med. 2021 Aug;22(2):905. doi: 10.3892/etm.2021.10337. Epub 2021 Jun 25.

ABSTRACT

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 pre sent 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).

PMID:34249152 | PMC:PMC8264823 | DOI:10.3892/etm.2021.10337

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Solitary Extramedullary Plasmacytoma of the Oropharynx: A Case Report

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Abstract

Plasma cell neoplasms rarely manifest as a solitary extramedullary plasmacytoma. Oropharyngeal involvement had been already reported in the literature. The most common malignancy of the oropharynx is squamous cell carcinoma, while soft tissue malignancy is extremely rare. In our present case report, the patient presented with a huge oropharyngeal mass which developed in a short duration. His family's concerns were mostly about his survival and quality of life. After complete checkup, a diagnosis for solitary extramedullary plasmacytoma of the oropharynx was concluded. The patient received neo-adjuvant chemotherapy and radiotherapy. The mass markedly decreased in size with complete regression as seen both clinically and radiologically. Our main aim for reporting this present case of pathology in oropharyngeal malignant masses is to increase the awareness and draw attention of Otolaryngology, the Head and Neck surgeons.

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Oral Malignant Melanoma

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Abstract

To present a case of malignant melanoma. A 55-year old female presented with swelling over left upper gingiva which bled on brushing. She was diagnosed with left oral malignant melanoma on histopathology of punch biopsy specimen, which was then followed by C.T. P.N.S and Neck to know the lesion's extent and Ultrasonography of Abdomen and Pelvis to rule out any metastatic deposits. Patient was managed by left lower partial maxillectomy with left radical neck dissection. No intra-operative or post-operative complications seen. Patient was then sent for chemoradiotherapy. No any complications seen at fifteen months follow-up. Oral malignant melanoma is amenable to surgery and chemoradiotherapy with excellent results if detected at an early stage.

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Study of Hearing Status in COVID-19 Patients: A Multicentered Review

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Abstract

To evaluate the hearing status of COVID-19 patients and compare with control group. Prospective study carried out in 9 institutes. The pure tone audiogram and impedance audiometry of COVID-19 patients performed initially and at 3 months follow up. The control group consisted COVID-19 negative individuals with no history of ear related diseases. The average of air and bone conduction threshold (AC and BC) were compared between the COVID-19 patients and control group using independent t-test with a p value of less than 0.05 considered significant. Total of 331 patients, age 32 ± 4.3 years, 66.7% males and 33.3% females were included in the study. There were 80 individuals in the control group. Aural symptoms were, tinnitus in 1.8%, aural fullness in 1.4%, hearing loss in 3. 9%, and ear ache in 1.8% were present initially, resolved at 3 months follow up. The impedance audiometry demonstrated type B and type C curve in 5.1% and 1.15% ears , and out of these 64.7% and 40% improved at 3 months follow up respectively. No significant difference observed between the average AC and BC of the COVID-19 patients and control group. The COVID-19 infection may present with aural symptoms; however, it was concluded that there was no significant difference in the hearing status of the COVID-19 positive patients in comparison to the control group. The presence of some changes in the normal functioning of the eustachian tube and middle ear in the COVID-19 infection was also highlighted.

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Lingual-Artery Thromboembolism

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An 83-year-old woman presented with swelling and discoloration of the right side of the tongue. An electrocardiogram revealed atrial fibrillation. CT angiography was performed, and a diagnosis of right lingual-artery thromboembolism was made.

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Long-term results of a balloon-assisted endoscopic approach in failed dacryocystorhinostomies

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Eur Arch Otorhinolaryngol. 2021 Jul 12. doi: 10.1007/s00405-021-06975-3. Online ahead of print.

ABSTRACT

PURPOSE: Endoscopic endonasal balloon-assisted dacryoplasty is a minimally invasive surgical approach that can be applied after failure of dacryocystorhinostomy with recurrence of distal acquired lacrimal obstruction.

METHODS: At the Department of Otolaryngology, San Raffaele Hospital, Milan (Italy), from December 2016 to October 2020, 14 patients underwent trans-nasal balloon-assisted dacryoplasty after a failed dacryocystorhinostomy (both external and endoscopic endonasal). The routinary pre-operative work-up included multidisciplinary study of the lacrimal disease, which consisted in primary ophthalmological and otorhinolaryngological visits associated with nasal endoscopy, in which a radiological exam was added if needed. The surgical approach includes pneumatic enlargement of the stenotic rhinostomy, created during the pr imary dacryocystorhinostomy, using a high-pressure trans-nasal balloon catheter. Anatomical success was considered when the ostium was patent upon irrigation, while functional success was considered as resolution of epiphora or free lacrimal flow on functional test.

RESULTS: Among 14 patients included and after a mean follow-up of 19.5 months (range 13-51 months), anatomic success was achieved in 100% of patients and functional success was achieved in the 85.7% (12/14). Operative time ranged from 9 to 28 min (mean 18 min) and no complications were reported.

CONCLUSION: Trans-nasal balloon-assisted dacryoplasty is a mini-invasive surgical approach to treat failed dacryocystorhinostomies with reliable and stable outcomes in the long term. The absence of post-surgical complications, high success rate and short operative time are the main features of this innovative procedure.

PMID:34251520 | DOI:10.1007/s00405-021-06975-3

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BCAT1 knockdown-mediated suppression of melanoma cell proliferation and migration is associated with reduced oxidative phosphorylation

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Am J Cancer Res. 2021 Jun 15;11(6):2670-2683. eCollection 2021.

ABSTRACT

Malignant melanoma has a high mutational rate. As a result, resistance to current therapies is common. Consequently, there is an unmet medical need to develop novel therapies. Recent data suggest that branched-chain amino acid transaminase 1 (BCAT1) is overexpressed in multiple cancers, and such overexpressed BCAT1 is necessary for individual cancer progression. Therefore, BCAT1 appears to be a good target in cancer treatment. Additionally, because its expression in healthy tissues is highly restricted in adults and is limited to the brain, ovary, and placenta, BCAT1 is especially an ideal target in cancer therapies. Currently, the function of BCAT1 in malignant melanoma has not been demonstrated. Therefore, we investigated the role of BCAT1 in the proliferation and migration of malignant melanomas using human samples and mouse malignant B16 melanoma cell line. Ou r data showed that BCAT1 was overexpressed in malignant melanoma tissues both in humans and mice. Besides, BCAT1 knockdown suppressed melanoma cell proliferation and migration, which was associated with reduced oxidative phosphorylation. Collectively, our data indicate that BCAT1 is a promising therapeutic target for the treatment of malignant melanomas.

PMID:34249421 | PMC:PMC8263658

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TAFs contributes the function of PTPN2 in colorectal carcinogenesis through activating JAK/STAT signaling pathway

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Am J Cancer Res. 2021 Jun 15;11(6):3085-3097. eCollection 2021.

ABSTRACT

The morbidity and mortality of colorectal cancer (CRC) ranks fourth worldwide, moreover, the tumor microenvironment (TME) of CRC is quite complex, and is one of the necessary factors affecting promotion of tumor metastasis. PTPN2 is a tumor suppressor which plays an important role in cancer-related downstream molecular pathway. FSP-1 is highly-expressed in multiple types of tumor tissues and is a biomarker of stromal fibroblasts. To examine the function of PTPN2 in the metastasis of CRC, the study evaluated the co-expression level of PTPN2 and FSP-1 in CRC tissues by double staining, and demonstrated the relationship with clinical information about each patient. The roles of PTPN2 and FSP-1 were detected in vitro by proliferation and transwell assay through knockdown of expression level of PTPN2. Lower PTPN2 with higher FSP-1 expression was correlated with poor survival outcomes in CRC. TAFs contribute to the migration function of PTPN2 in CRC in vitro through inducing changes in the level of TGF-β1. Western blot and qRT-PCR assays were used to detect the mechanism of PTPN2 regulation of migration with TAFs in the JAK/STAT signaling pathway, moreover, TAFs contributed the function of PTPN2 in colorectal carcinogenesis in vivo. In summary, the study shed light on the effect of TAFs contributes the function of PTPN2 in colorectal carcinogenesis through activating JAK/STAT signaling pathway. In addition, double-staining assay could give us a unique perspective from which to study TME in CRC.

PMID:34249446 | PMC:PMC8263690

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Mortalin maintains breast cancer stem cells stemness via activation of Wnt/GSK3beta/beta-catenin signaling pathway

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Am J Cancer Res. 2021 Jun 15;11(6):2696-2716. eCollection 2021.

ABSTRACT

Previous research indicated that mortalin overexpressed in breast cancer and contributed to carcinogenesis. Mortalin was also demonstrated to promote Epithelial-mesenchymal transition (EMT) and was considered as a factor for maintaining the stemness of the cancer stem cells. However, the underlying mechanisms about mortalin maintaining the stemness of breast cancer stem cells (BCSCs) remain unclear. Here, we identified that increased expression of mortalin in breast cancer was associated with poorer overall survival rate. Mortalin was elevated in breast cancer cell lines and BCSC-enriched populations. Additionally, knockdown of mortalin significantly inhibited the cell proliferation, migration and EMT, as well as sphere forming capacity and stemness genes expression. Further study revealed that mortalin promoted EMT and maintained BCSCs stemness via activating the Wnt/GSK3β/β-catenin signaling pathway in vivo and in vitro. Taken together, these findings unveiled the mechanism of mortalin in maintaining and regulating the stemness of BCSCs, and may offer novel therapeutic strategies for breast cancer treatment.

PMID:34249423 | PMC:PMC8263651

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Monepantel antitumor activity is mediated through inhibition of major cell cycle and tumor growth signaling pathways

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Am J Cancer Res. 2021 Jun 15;11(6):3098-3110. eCollection 2021.

ABSTRACT

In women, epithelial ovarian cancer is the leading cause of gynaecological malignancy-related deaths. Development of resistance to standard platinum and taxane based chemotherapy and recurrence of the disease necessitate development of novel drugs to halt disease progression. An established concept is to target molecular and signaling pathways that substantially contribute to development of drug resistance and disease progression. We have previously shown that, monepantel (MPL) a novel small molecule acetonitrile derivative is highly effective in suppressing growth, proliferation and colony formation of ovarian cancer cells. These effects are achieved through inhibition of the mTOR/p70S6K pathway in cancer cells. The present study was conducted to find in vivo corroboration and explore the effect of MPL om other growth stimulating putative signaling pathways. Here , female nude mice with subcutaneous OVCAR-3 xenografts were treated with 25 and 50 mg/kg doses of MPL administered (IP) three times weekly for 2 weeks. At the doses employed, MPL was modestly effective at suppressing tumor growth, but highly effective in inhibiting, mTOR, P70S6K and 4EBP1. There were also modest reductions in tumor cyclin D1 and retinoblastoma protein expression. Furthermore, it was found that MPL treatment causes down-regulation of IGF-1R, and c-MYC thus unveiling new dimensions to the growing antitumor actions of this potential anticancer drug. MPL treatment led to reduced tumor volume and weights without causing any detectable side effects. Coupled with the recent human safety data published on this molecule, expanded future trials are highly anticipated.

PMID:34249447 | PMC:PMC8263694

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Blood-based risk stratification for pre-malignant and symptomatic plasma cell neoplasms to improve patient management

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Am J Cancer Res. 2021 Jun 15;11(6):2736-2753. eCollection 2021.

ABSTRACT

Standard risk stratification (sRisk) guides clinical management in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and multiple myeloma (MM). Nonetheless, clinical results are considerably heterogeneous among patients with similar risk status. Blood and bone marrow samples from 276 MGUS, 56 SMM and 242 MM in regular clinical practice were analyzed at diagnosis by flow cytometry. Higher levels of aberrant circulating plasma cells (cPC) (> 0.0035% of leukocytes), combined with albumin, beta2-microglobuline and lactate-dehydrogenase levels, offered minimally-invasive risk stratification (RcPC) with results comparable to sRisk. RcPC and sRisk 10-year progression-free-survival (10y-PFS) rates were: 93.8% vs. 95.1% for low-risk, 78.4% vs. 81.7% for intermediate-risk and 50.0% vs. 47.8% for high-risk MGUS; 58.3% vs. 57.8% l ow-risk, 44.4% vs. 45.8% intermediate-risk and 8.9% vs. 15.0% high-risk SMM; and 44.4% vs. 44.4% low-risk, 36.1% vs. 36.8% intermediate-risk, and 13.3% vs. 16.2% high-risk MM. Circulating-PC > 0.0035% vs. cPC<0.0035% was an independent prognostic factor for PFS (HR=4.389, P=1.2×10-15, Harrell C-statistic =0.7705±0.0190) and over-all survival (OS, HR=4.286, 2.3×10-9, Harrell C-statistic =0.8225±0.0197) that complemented sRisk in patients with low-sRisk (10y-PFS rates 48.1% vs. 87.3%, P=1.2×10-8) and intermediate-sRisk (10y-PFS rates 28.9% vs. 74.1%, P=8.6×10-12). Patients with high cPCs values are associated with higher proliferation and lower apoptosis rates of PC. Circulating-PC > 0.0035% identified MGUS, SMM and MM patients at higher risk of progression or death and predicted a cohort of patients that after relapse from stringent complete response showed shorter OS. These patients could benefit from early consolidation the rapy, tandem ASCT or intensive maintenance.

PMID:34249425 | PMC:PMC8263680

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