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Applied Immunohistochemistry &... Sep 2021Programmed death-1 (PD1) expression has not been reported in gallbladder adenocarcinoma. In this study we examined PD1 expression in gallbladder cancer to explore the...
Programmed death-1 (PD1) expression has not been reported in gallbladder adenocarcinoma. In this study we examined PD1 expression in gallbladder cancer to explore the correlation between PD1 expression and the clinicopathologic parameters. We found that 98% (46/47) cases expressed programmed death-ligand 1 (PD-L1) with 85% cases being PD-L1 3+. PD1+ tumor-infiltrating lymphocytes (TILs) were present in 78.7% cases (37/47). The tumor size was significantly smaller and the stromal CD3+ TILs were significantly higher in tumors with PD1+ TILs than those with PD1- TILs. In the tumors with size of <3 cm, stromal CD3+ TILs >115/HPF or stromal CD8+ TILs >45/HPF were associated with much better survival than those with stromal CD3+ TILs ≤115/HPF or stromal CD8+ TILs ≤45/HPF. In tumors with the size of 3 cm or larger, PD1+ TILs or stromal CD8+ TILs >45/HPF carried a significantly poorer survival than PD1- tumors or stromal CD8+ TILs <=45/HPF. No correlation was identified between PD1 expression and lymphovascular invasion, distant metastasis, pathologic tumor stage or prognostic stage. Multivariate survival analysis showed that tumor TNM stage and age were independent prognostic factors in gallbladder adenocarcinomas. We conclude that gallbladder adenocarcinomas may have high PD-L1 expression and PD1+ TILs. Smaller tumor size and greater amount of stromal CD3+ T cells were found in tumors with PD1+ TILs. In small tumors (<3 cm), high stromal CD3+ TILs or high stromal CD8+ TILs were associated with better survival. However, in large tumors (≥3 cm), PD1+ TILs or high stromal CD8+ TILs carried a poorer survival. Our study implied that immune-based therapy including PD1/PD-L1 checkpoint blockade might be useful in gallbladder adenocarcinomas.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; B7-H1 Antigen; CD8-Positive T-Lymphocytes; Female; Gallbladder Neoplasms; Humans; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Retrospective Studies; Tumor Microenvironment
PubMed: 33710123
DOI: 10.1097/PAI.0000000000000922 -
British Journal of Cancer Jan 2021Although substantial progress has been made over the past 40 years in treating patients with cancer, effective therapies for those who are diagnosed with advanced... (Review)
Review
Although substantial progress has been made over the past 40 years in treating patients with cancer, effective therapies for those who are diagnosed with advanced metastatic disease are still few and far between. Cancer cells do not exist in isolation: rather, they exist within a complex microenvironment composed of stromal cells and extracellular matrix. Within this tumour microenvironment exists an interplay between the two main stromal cell subtypes, cancer-associated fibroblasts (CAFs) and immune cells, that are important in controlling metastasis. A complex network of paracrine signalling pathways between CAFs, immune cells and tumour cells are involved at multiple stages of the metastatic process, from invasion and intravasation at the primary tumour site to extravasation and colonisation in the metastatic site. Heterogeneity and plasticity within stromal cell populations also contribute to the complexity. Although many of these processes are likely to be common to a number of metastatic sites, we will describe in detail the interplay within the liver, a preferred site of metastasis for many tumours. A greater understanding of these networks provides opportunities for the design of new therapeutic approaches for targeting the metastatic disease.
Topics: Animals; Cancer-Associated Fibroblasts; Fibrosis; Humans; Liver; Neoplasm Invasiveness; Neoplasms; Tumor Microenvironment
PubMed: 33239677
DOI: 10.1038/s41416-020-01172-1 -
International Journal of Gynecological... Jun 2023Uterine sarcomas are a rare and heterogeneous group of malignancies that include different histological sub-types. The aim of this study was to identify and evaluate the...
OBJECTIVE
Uterine sarcomas are a rare and heterogeneous group of malignancies that include different histological sub-types. The aim of this study was to identify and evaluate the impact of the different prognostic factors on overall survival and disease-free survival of patients with uterine sarcoma.
METHODS
This international multicenter retrospective study included 683 patients diagnosed with uterine sarcoma at 46 different institutions between January 2001 and December 2007.
RESULTS
The 5-year overall survival for leiomyosarcoma, endometrial stromal sarcoma, undifferentiated sarcoma, and adenosarcoma was 65.3%, 78.3%, 52.4%, and 89.5%, respectively, and the 5-year disease-free survival was 54.3%, 68.1%, 40.3%, and 85.3%, respectively. The 10-year overall survival for leiomyosarcoma, endometrial stromal sarcoma, undifferentiated sarcoma and adenosarcoma was 52.6%, 64.8%, 52.4%, and 79.5%, respectively, and the 10-year disease-free survival was 44.7%, 53.3%, 40.3%, and 77.5%, respectively. The most significant factor associated with overall survival in all types of sarcoma except for adenosarcoma was the presence of residual disease after primary treatment. In adenosarcoma, disease stage at diagnosis was the most important factor (hazard ratio 17.7; 95% CI 2.86 to 109.93).
CONCLUSION
Incomplete cytoreduction, tumor persistence, advanced stage, extra-uterine and tumor margin involvement, and the presence of necrosis were relevant prognostic factors significantly affecting overall survival in uterine sarcoma. The presence of lymph vascular space involvement and administration of adjuvant chemotherapy were significantly associated with a higher risk of relapse.
Topics: Female; Humans; Leiomyosarcoma; Adenosarcoma; Prognosis; Sarcoma, Endometrial Stromal; Retrospective Studies; Neoplasm Recurrence, Local; Sarcoma; Uterine Neoplasms; Pelvic Neoplasms; Endometrial Neoplasms
PubMed: 37192761
DOI: 10.1136/ijgc-2022-004204 -
Histopathology May 2022Microcystic stromal tumour (MST) is a rare, usually benign, ovarian neoplasm characterized morphologically in its classic form by a distinctive triad of features... (Review)
Review
Microcystic stromal tumour (MST) is a rare, usually benign, ovarian neoplasm characterized morphologically in its classic form by a distinctive triad of features comprising microcysts, solid cellular regions and fibrous stroma. Variant morphology also occurs, including the presence of nests, tubules, cords and signet ring cells. Immunohistochemically, this neoplasm is characterized by diffuse nuclear expression of β-catenin, cyclin D1, Wilms' tumour 1 (WT1) and steroidogenic factor 1 (SF1), as well as diffuse staining with forkhead box ligand 2 (FoxL2) and CD10. Inhibin and calretinin are typically negative. At the genomic level, these neoplasms harbour mutually exclusive mutations in CTNNB1 or APC genes, with the former being significantly more common. This molecular characteristic raises possible links to other rare ovarian lesions, including solid pseudopapillary tumour, signet-ring stromal tumour and Sertoli cell tumour. Rarely, MST is an extracolonic manifestation of familial adenomatous polyposis (FAP) and serves as a sentinel event that could trigger the identification of the syndrome. Herein, we review the published literature on ovarian MST and provide practical advice for pathologists reporting these rare neoplasms.
Topics: Biomarkers, Tumor; DNA Mutational Analysis; Female; Humans; Immunohistochemistry; Ovarian Cysts; Ovarian Neoplasms; Sex Cord-Gonadal Stromal Tumors; beta Catenin
PubMed: 35020947
DOI: 10.1111/his.14616 -
Acta Biomaterialia Sep 2021Glioblastoma multiforme (GBM) is the most deadly form of brain cancer. Recurrence is common, and established therapies have not been able to significantly extend overall... (Review)
Review
Glioblastoma multiforme (GBM) is the most deadly form of brain cancer. Recurrence is common, and established therapies have not been able to significantly extend overall patient survival. One platform through which GBM research can progress is to design biomimetic systems for discovery and investigation into the mechanisms of invasion, cellular properties, as well as the efficacy of therapies. In this review, 2D and 3D GBM in vitro cultures will be discussed. We focus on the effects of biomaterial properties, interactions between stromal cells, and vascular influence on cancer cell survival and progression. This review will summarize critical findings in each of these areas and how they have led to a more comprehensive scientific understanding of GBM. STATEMENT OF SIGNIFICANCE: Glioblastoma multiforme (GBM) is the most deadly form of brain cancer. Recurrence is common, and established therapies have not been able to significantly extend overall patient survival. One platform through which GBM research can progress is to design biomimetic systems for discovery and investigation into the mechanisms of invasion, cellular properties, as well as the efficacy of therapies. In this review, 2D and 3D GBM in vitro cultures will be discussed. We focus on the effects of biomaterial properties, interactions between stromal cells and vascular influence on cancer cell survival and progression. This review will summarize critical findings in each of these areas and how they have lead to a more comprehensive scientific understanding of GBM.
Topics: Biocompatible Materials; Brain Neoplasms; Cell Line, Tumor; Glioblastoma; Humans; Hydrogels; Neoplasm Recurrence, Local; Stromal Cells; Tumor Microenvironment
PubMed: 33276155
DOI: 10.1016/j.actbio.2020.11.044 -
Seminars in Nephrology Jan 2024End-stage kidney disease patients who are referred for transplant undergo an extensive evaluation process to ensure their health prior to transplant due in part to the... (Review)
Review
End-stage kidney disease patients who are referred for transplant undergo an extensive evaluation process to ensure their health prior to transplant due in part to the shortage of available organs. Although management and surveillance guidelines exist for malignancies identified in the transplant and waitlist populations, less is written about the management of premalignant lesions in this population. This review covers the less common premalignant lesions (intraductal papillary mucinous neoplasm, gastrointestinal stromal tumor, thymoma, and pancreatic neuroendocrine tumor) that can be found in the transplant candidate population. High-level evidence for the management of these rarer premalignant lesions in the transplant population is lacking, and this review extrapolates evidence from the general population and should not be a substitute for a multidisciplinary discussion with medical and surgical oncologists.
Topics: Humans; Kidney Transplantation; Precancerous Conditions; Kidney Failure, Chronic; Gastrointestinal Stromal Tumors; Thymoma; Pancreatic Neoplasms; Thymus Neoplasms
PubMed: 38490902
DOI: 10.1016/j.semnephrol.2024.151495 -
Seminars in Cell & Developmental Biology Oct 2019Precise intracellular calcium signaling is crucial to numerous cellular functions. In non-excitable cells, store-operated calcium entry (SOCE) is a key step in the... (Review)
Review
Precise intracellular calcium signaling is crucial to numerous cellular functions. In non-excitable cells, store-operated calcium entry (SOCE) is a key step in the generation of intracellular calcium signals. Tight regulation of SOCE is important, and dysregulation is involved in several pathophysiological cellular malfunctions. The current underlying SOCE, calcium release-activated calcium current (I), was first discovered almost three decades ago. Since its discovery, the molecular components of I, Orai1 and stromal interaction molecule 1 (STIM1), have been extensively investigated. Several regulatory mechanisms and proteins contribute to alterations in SOCE and cellular malfunctions in cancer, immune and neurodegenerative diseases, inflammation, and neuronal disorders. This review summarizes these regulatory mechanisms, including glycosylation, pH sensing, and the regulatory proteins golli, α-SNAP, SARAF, ORMDL3, CRACR2A, and TRPM4 channels.
Topics: Animals; Calcium; Calcium Signaling; Humans; Inflammation; Neoplasm Proteins; Neoplasms; Neurodegenerative Diseases; ORAI1 Protein; Stromal Interaction Molecule 1
PubMed: 30630032
DOI: 10.1016/j.semcdb.2019.01.003 -
Japanese Journal of Clinical Oncology Feb 2024Esophageal cancer is common worldwide, including in Japan, and its major histological subtype is squamous cell carcinoma. However, there are some rare esophageal... (Review)
Review
Esophageal cancer is common worldwide, including in Japan, and its major histological subtype is squamous cell carcinoma. However, there are some rare esophageal cancers, including neuroendocrine neoplasm, gastrointestinal stromal tumor, carcinosarcoma and malignant melanoma. The biological and clinical features of these cancers differ from those of esophageal squamous cell carcinoma. Therefore, different treatment strategies are needed for these cancers but are based on limited evidence. Neuroendocrine neoplasm is mainly divided into neuroendocrine tumor and neuroendocrine carcinoma by differentiation and the Ki-67 proliferation index or mitotic index. Epidemiologically, the majority of esophageal neuroendocrine neoplasms are neuroendocrine carcinoma. The treatment of neuroendocrine carcinoma is similar to that of small cell lung cancer, which has similar morphological and biological features. Gastrointestinal stromal tumor is known to be associated with alterations in the c-KIT and platelet-derived growth factor receptor genes and, if resectable, is treated in accordance with the modified Fletcher classification. Carcinosarcoma is generally resistant to both chemotherapy and radiotherapy and requires multimodal treatments such as surgery plus chemotherapy to achieve cure. Primary malignant melanoma is resistant to cytotoxic chemotherapy, but immune checkpoint inhibitors have recently demonstrated efficacy for malignant melanoma of the esophagus. This review focuses on the current status and future perspectives for rare cancer of the esophagus.
Topics: Humans; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Melanoma; Carcinoma, Neuroendocrine; Gastrointestinal Stromal Tumors; Carcinosarcoma
PubMed: 37861097
DOI: 10.1093/jjco/hyad144 -
Frontiers in Immunology 2021Cancer-associated fibroblasts (CAFs) are the most important component of the stromal cell population in the tumor microenvironment and play an irreplaceable role in... (Review)
Review
Cancer-associated fibroblasts (CAFs) are the most important component of the stromal cell population in the tumor microenvironment and play an irreplaceable role in oncogenesis and cancer progression. Exosomes, a class of small extracellular vesicles, can transfer biological information (e.g., proteins, nucleic acids, and metabolites as messengers) from secreting cells to target recipient cells, thereby affecting the progression of human diseases, including cancers. Recent studies revealed that CAF-derived exosomes play a crucial part in tumorigenesis, tumor cell proliferation, metastasis, drug resistance, and the immune response. Moreover, aberrant expression of CAF-derived exosomal noncoding RNAs and proteins strongly correlates with clinical pathological characterizations of cancer patients. Gaining deeper insight into the participation of CAF-derived exosomes in tumorigenesis may lead to novel diagnostic biomarkers and therapeutic targets in human cancers.
Topics: Animals; Biological Transport; Cancer-Associated Fibroblasts; Cell Transformation, Neoplastic; Disease Susceptibility; Drug Resistance, Neoplasm; Energy Metabolism; Exosomes; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Signal Transduction
PubMed: 35058933
DOI: 10.3389/fimmu.2021.795372 -
International Journal of Molecular... Feb 2021Despite improvements in therapy and management, cancer represents and remains a major cause of mortality and morbidity worldwide. Although genetics serve an important... (Review)
Review
Despite improvements in therapy and management, cancer represents and remains a major cause of mortality and morbidity worldwide. Although genetics serve an important role in tumorigenesis and tumour progression, the tumour microenvironment (TME) in solid tumours is also important and has been indicated to contribute to these processes. Stromal cell‑derived factors (SDFs) represent an important family within the TME. The family includes SDF‑1, SDF‑2, SDF2‑like 1 (SDF2L1), SDF‑3, SDF‑4 and SDF‑5. SDF‑1 has been demonstrated to act as a positive regulator in a number of types of tumour, such as oesophago‑gastric, pancreatic, lung, breast, colorectal and ovarian cancer, while the biology and functions of other members of the SDF family, including SDF‑2, SDF2L1, SDF‑4 and SDF‑5, in cancer are different, complex and controversial, and remain mainly unknown. Full identification and understanding of the SDFs across multiple types of cancer is required to elucidate their function and establish potential key targets in cancer.
Topics: Humans; Intercellular Signaling Peptides and Proteins; Neoplasm Proteins; Neoplasms; Tumor Microenvironment
PubMed: 33416125
DOI: 10.3892/ijmm.2020.4811