Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors

Mesothelin (MSLN) represents an attractive molecule for targeted cancer therapies. To identify tumors that might benefit from such therapies, tissue microarrays including 15,050 tumors from 122 different tumor types and 76 healthy organs were analyzed for MSLN expression by immunohistochemistry. Sixty-six (54%) tumor types showed at least occasional weak staining, including 50 (41%) tumor types with at least one strongly positive sample. Highest prevalence of MSLN positivity had ovarian carcinomas (serous 97%, clear cell 83%, endometrioid 77%, mucinous 71%, carcinosarcoma 65%), pancreatic adenocarcinoma (ductal 75%, ampullary 81%), endometrial carcinomas (clear cell 71%, serous 57%, carcinosarcoma 50%, endometrioid 45%), malignant mesothelioma (69%), and adenocarcinoma of the lung (55%). MSLN was rare in cancers of the breast (7% of 1138), kidney (7% of 807), thyroid gland (1% of 638), soft tissues (0.3% of 931), and prostate (0 of 481). High expression was linked to advanced pathological tumor (pT) stage (p < 0.0001) and metastasis (p < 0.0001) in 1619 colorectal adenocarcinomas, but unrelated to parameters of malignancy in 1072 breast-, 386 ovarian-, 174 lung-, 757 kidney-, 171 endometrial-, 373 gastric-, and 925 bladder carcinomas. In summary, numerous important cancer types with high-level MSLN expression might benefit from future anti-MSLN therapies, but MSLN’s prognostic relevance appears to be limited.

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Role of POT1 in Human Cancer

Cancers ◽

10.3390/cancers12102739 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2739 ◽

Cited By ~ 2

Author(s):

Yangxiu Wu ◽

Rebecca C. Poulos ◽

Roger R. Reddel

Keyword(s):

Human Cancer ◽

Cell Types ◽

Cancer Therapies ◽

Telomeric Dna ◽

Targeted Cancer Therapies ◽

Length Regulation ◽

Tumor Types ◽

Different Cell Types ◽

Essential Subunit

Telomere abnormalities facilitate cancer development by contributing to genomic instability and cellular immortalization. The Protection of Telomeres 1 (POT1) protein is an essential subunit of the shelterin telomere binding complex. It directly binds to single-stranded telomeric DNA, protecting chromosomal ends from an inappropriate DNA damage response, and plays a role in telomere length regulation. Alterations of POT1 have been detected in a range of cancers. Here, we review the biological functions of POT1, the prevalence of POT1 germline and somatic mutations across cancer predisposition syndromes and tumor types, and the dysregulation of POT1 expression in cancers. We propose a framework for understanding how POT1 abnormalities may contribute to oncogenesis in different cell types. Finally, we summarize the clinical implications of POT1 alterations in the germline and in cancer, and possible approaches for the development of targeted cancer therapies.

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Molecular stratification of clear cell ovarian carcinomas

10.1055/s-0040-1718135 ◽

2020 ◽

Author(s):

L Feil ◽

J Senz ◽

M Ta ◽

J Huvila ◽

K Greif ◽

...

Keyword(s):

Clear Cell ◽

Ovarian Carcinomas ◽

Molecular Stratification

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91 Retinopathy Secondary to Targeted Cancer Therapies

The Retina Illustrated ◽

10.1055/b-0040-174276 ◽

2020 ◽

Keyword(s):

Cancer Therapies ◽

Targeted Cancer Therapies

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Mismatch repair deficiency is associated with specific morphologic features and frequent loss of ARID1A expression in ovarian clear cell carcinoma

Diagnostic Pathology ◽

10.1186/s13000-021-01071-w ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Huijuan Ge ◽

Yaoxin Xiao ◽

Guangqi Qin ◽

Yanzi Gu ◽

Xu Cai ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Tumor Infiltrating Lymphocytes ◽

Tissue Microarrays ◽

Ovarian Clear Cell Carcinoma ◽

Repair Deficiency ◽

Ovarian Epithelial Carcinoma ◽

Histological Characteristics ◽

Infiltrating Lymphocytes

Abstract Background Ovarian clear cell carcinoma (OCCC) is the second subtype of ovarian epithelial carcinoma reported to be closely related to Lynch syndrome (LS). ARID1A mutation is an important pathogenetic mechanism in OCCC that leads to loss of ARID1A expression in approximately half of OCCCs. However, the correlation of MMR status and ARID1A deficiency is unclear. The current study aimed to identify the clinical and histopathological characteristics of OCCC associated with dMMR and to further explore the association between dMMR and ARID1A deficiency. Methods A cohort of 176 primary OCCC patients was enrolled and review included histological characteristics (nuclear atypia, necrosis, mitosis, stromal hyalinization, and background precursors) and host inflammatory response (tumor-infiltrating lymphocytes, peritumoral lymphocytes, intratumoral stromal inflammation and plasma cell infiltration). Immunohistochemical staining of MLH1, PMS2, MSH2, MSH6 and ARID1A was performed using tissue microarrays. Results dMMR was detected in 10/176 tumors (6 %), followed by MSH2/MSH6 (6/176), MLH1/PMS2 (3/176), and MSH6 (1/176). The average age of patients with dMMR was younger than that of patients with intact MMR (46 y vs. 53 y). Tumors with diffuse intratumoral stromal inflammation remained significantly associated after multivariate analysis. ARID1A expression was absent in 8 patients with dMMR (8/10), which is a significantly higher frequency than that observed in patients with intact MMR (80 % vs. 43.2 %). Conclusions Our study indicates that diffuse intratumoral stromal inflammation of OCCCs is associated with dMMR, with loss of MSH2/MSH6 expression being most frequent. dMMR is strongly associated with the loss of ARID1A expression in OCCC.

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Photodynamic Therapy Combined with Antibiotics or Antifungals against Microorganisms That Cause Skin and Soft Tissue Infections: A Planktonic and Biofilm Approach to Overcome Resistances

Pharmaceuticals ◽

10.3390/ph14070603 ◽

2021 ◽

Vol 14 (7) ◽

pp. 603

Author(s):

Vanesa Pérez-Laguna ◽

Isabel García-Luque ◽

Sofía Ballesta ◽

Antonio Rezusta ◽

Yolanda Gilaberte

Keyword(s):

Photodynamic Therapy ◽

Soft Tissues ◽

Combined Treatment ◽

Resistance Pattern ◽

Antimicrobial Photodynamic Therapy ◽

Antimicrobial Drugs ◽

Bacteria And Fungi ◽

High Level ◽

Selection Of

The present review covers combination approaches of antimicrobial photodynamic therapy (aPDT) plus antibiotics or antifungals to attack bacteria and fungi in vitro (both planktonic and biofilm forms) focused on those microorganisms that cause infections in skin and soft tissues. The combination can prevent failure in the fight against these microorganisms: antimicrobial drugs can increase the susceptibility of microorganisms to aPDT and prevent the possibility of regrowth of those that were not inactivated during the irradiation; meanwhile, aPDT is effective regardless of the resistance pattern of the strain and their use does not contribute to the selection of antimicrobial resistance. Additive or synergistic antimicrobial effects in vitro are evaluated and the best combinations are presented. The use of combined treatment of aPDT with antimicrobials could help overcome the difficulty of fighting high level of resistance microorganisms and, as it is a multi-target approach, it could make the selection of resistant microorganisms more difficult.

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Senolytics for Cancer Therapy: Is All that Glitters Really Gold?

Cancers ◽

10.3390/cancers13040723 ◽

2021 ◽

Vol 13 (4) ◽

pp. 723

Author(s):

Valerie J. Carpenter ◽

Tareq Saleh ◽

David A. Gewirtz

Keyword(s):

Cancer Therapy ◽

Tumor Cell ◽

Cancer Therapies ◽

Cell Models ◽

Future Directions ◽

Targeted Cancer Therapies

Senolytics represent a group of mechanistically diverse drugs that can eliminate senescent cells, both in tumors and in several aging-related pathologies. Consequently, senolytic use has been proposed as a potential adjuvant approach to improve the response to senescence-inducing conventional and targeted cancer therapies. Despite the unequivocal promise of senolytics, issues of universality, selectivity, resistance, and toxicity remain to be further clarified. In this review, we attempt to summarize and analyze the current preclinical literature involving the use of senolytics in senescent tumor cell models, and to propose tenable solutions and future directions to improve the understanding and use of this novel class of drugs.

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