Components of the Hematopoietic Compartments in Tumor Stroma and Tumor-Bearing Mice

Solid tumors are composed of cancerous cells and non-cancerous stroma. A better understanding of the tumor stroma could lead to new therapeutic applications. However, the exact compositions and functions of the tumor stroma are still largely unknown. Here, using a Lewis lung carcinoma implantation mouse model, we examined the hematopoietic compartments in tumor stroma and tumor-bearing mice. Different lineages of differentiated hematopoietic cells existed in tumor stroma with the percentage of myeloid cells increasing and the percentage of lymphoid and erythroid cells decreasing over time. Using bone marrow reconstitution analysis, we showed that the tumor stroma also contained functional hematopoietic stem cells. All hematopoietic cells in the tumor stroma originated from bone marrow. In the bone marrow and peripheral blood of tumor-bearing mice, myeloid populations increased and lymphoid and erythroid populations decreased and numbers of hematopoietic stem cells markedly increased with time. To investigate the function of hematopoietic cells in tumor stroma, we co-implanted various types of hematopoietic cells with cancer cells. We found that total hematopoietic cells in the tumor stroma promoted tumor development. Furthermore, the growth of the primary implanted Lewis lung carcinomas and their metastasis were significantly decreased in mice reconstituted with IGF type I receptor-deficient hematopoietic stem cells, indicating that IGF signaling in the hematopoietic tumor stroma supports tumor outgrowth. These results reveal that hematopoietic cells in the tumor stroma regulate tumor development and that tumor progression significantly alters the host hematopoietic compartment

MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma

MicroRNAs (miRs) are expected to serve as prognostic tools for cancer. However, many miRs have been reported as prognostic markers of recurrence or metastasis in oral squamous cell carcinoma patients. We aimed to determine the prognostic markers in early‑stage tongue squamous cell carcinoma (TSCC). Based on previous studies, we hypothesized that miR‑10a, 10b, 196a‑5p, 196a‑3p, and 196b were prognostic markers and we retrospectively performed miR expression analyses using formalin‑fixed paraffin‑embedded sections of surgical specimens. Total RNA was isolated from cancer tissues and adjacent normal tissue as control, and samples were collected by laser‑capture microdissection. After cDNA synthesis, reverse transcription‑quantitative polymerase chain reaction was performed. Statistical analyses for patient clinicopathological characteristics, recurrence/metastasis, and survival rates were performed to discern their relationships with miR expression levels, and the 2‑ΔΔCq method was used. miR‑196a‑5p levels were significantly upregulated in early‑stage TSCC, particularly in the lymph node metastasis (LNM) group. The LNM‑free survival rate in the low miR‑196a‑5p ΔΔCq value regulation group was found to be lower than that in the high ΔΔCq value regulation group (P=0.0079). Receiver operating characteristic analysis of ΔΔCq values revealed that miR‑196a‑5p had a P‑value=0.0025, area under the curve=0.740, and a cut‑off value=‑0.875 for distinguishing LNM. To our knowledge, this is the first study to examine LNM‑related miRs in early‑stage TSCC as well as miRs and ‘delayed LNM’ in head and neck cancer. miR‑196a‑5p upregulation may predict delayed LNM. Our data serve as a foundation for future studies to evaluate miR levels and facilitate the prediction of delayed LNM during early‑stage TSCC, which prevent metastasis when combined with close follow‑up and aggressive adjuvant therapy or elective neck dissection. Moreover, our data will serve as a foundation for future studies to evaluate whether miR‑196a‑5p can serve as a therapeutic marker for preventing metastasis

Components of the Hematopoietic Compartments in Tumor Stroma and Tumor-Bearing Mice

Solid tumors are composed of cancerous cells and non-cancerous stroma. A better understanding of the tumor stroma could lead to new therapeutic applications. However, the exact compositions and functions of the tumor stroma are still largely unknown. Here, using a Lewis lung carcinoma implantation mouse model, we examined the hematopoietic compartments in tumor stroma and tumor-bearing mice. Different lineages of differentiated hematopoietic cells existed in tumor stroma with the percentage of myeloid cells increasing and the percentage of lymphoid and erythroid cells decreasing over time. Using bone marrow reconstitution analysis, we showed that the tumor stroma also contained functional hematopoietic stem cells. All hematopoietic cells in the tumor stroma originated from bone marrow. In the bone marrow and peripheral blood of tumor-bearing mice, myeloid populations increased and lymphoid and erythroid populations decreased and numbers of hematopoietic stem cells markedly increased with time. To investigate the function of hematopoietic cells in tumor stroma, we co-implanted various types of hematopoietic cells with cancer cells. We found that total hematopoietic cells in the tumor stroma promoted tumor development. Furthermore, the growth of the primary implanted Lewis lung carcinomas and their metastasis were significantly decreased in mice reconstituted with IGF type I receptor-deficient hematopoietic stem cells, indicating that IGF signaling in the hematopoietic tumor stroma supports tumor outgrowth. These results reveal that hematopoietic cells in the tumor stroma regulate tumor development and tha

Quadruple Multiple Primary Malignancies: Early Detection of Second Primary Malignancy by Esophagogastroduodenoscopy/Colonoscopy Is Crucial for Patients with Classic Kaposi’s Sarcoma

Currently, Kaposi’s sarcoma (KS) is treated following the recommendations of international guidelines. These guidelines recommend esophagogastroduodenoscopy/colonoscopy for detecting multicentric KS of visceral lesions. Second primary malignancies (SPMs) are also a common KS complication; however, information on their detection and treatment is unfortunately not yet indicated in these guidelines. This paper reports on an 86-year-old man who suffered from quadruple primary malignancies: skin classic KS with colon adenocarcinoma, oral squamous cell carcinoma (maxilla), and well-differentiated stomach adenocarcinoma. Gastric cancer was incidentally detected during esophagogastroduodenoscopy, which was performed to detect visceral KS. We suggest that esophagogastroduodenoscopy/colonoscopy be routinely performed during the follow-up of patients with KS. As SPMs are crucial complications in patients with KS, these malignancies should be detected as early as possible