ABSTRACT
Squamous cell carcinoma (SCC) transformation of lung adenocarcinoma has been reported to take place after target therapy resistance. The patterns and mechanisms underlying this phenomenon needs to be explored. We present two such patients here. One patient complained of cough and hemoptysis, the other experienced chest tightness. Both were diagnosed as lung adenocarcinoma. They harbored no driver gene alterations and received first-line and adjuvant chemotherapy respectively. After progression several months later, the second biopsy revealed SCC transformation and the gene test still found no gene abnormalities. The diseases stayed stable after treatment of new therapeutic regimens. Then we searched for literature related and found SCC transformation happened at resistance to target therapy or immunotherapy or spontaneously. Our cases suggested this phenomenon could also happen at resistance to cytotoxic drugs. According to the reported cases, a new target therapy or chemotherapy might be effective after SCC transformation. The mechanisms underlying transformation have not been fully elucidated and probably relate to multiple genetic alterations and cancer stem cells. Since the SCC transformation could happen under various circumstances, we recommend lung cancer patients to run the second biopsy after progression and conduct gene tests to elicit the mechanisms.
ABSTRACT
The normal thymus contributes to T lymphocytes differentiation and induction of tolerance to self-antigens. Myasthenia gravis (MG) is characterized by abnormal thymic hyperplasia. To assess the potential influence of MG-thymus on the differentiation of T lymphocytes differentiation, we used the MG-thymus transplanted severe combined immunodeficiency (SCID) mice model to evaluate the human cord blood stem cells differentiation. Thymus fragments from MG patient and human cord blood stem cells were transplanted into SCID mice successively. SCID mice were observed to develop sustained human T lymphocytes and a functional anti-tumor immune. The levels of various T cell subsets in SCID mice with MG-thymus were different from that of control group. Among that, the frequency of CD4(+)CD25(+) T cells was significant lower in SCID mice with MG-thymus. The deficiency of CD4(+)CD25(+) T cells seens to contribute to the pathogenesis of MG.
Subject(s)
Hematopoietic Stem Cells/physiology , Lymphopoiesis , Myasthenia Gravis/physiopathology , T-Lymphocytes/physiology , Thymus Gland/physiopathology , Animals , Antigens, CD34/metabolism , CD4-Positive T-Lymphocytes/physiology , Cell Line, Tumor , Fetal Blood , Flow Cytometry , Hematopoietic Stem Cell Transplantation , Humans , Immunohistochemistry , Male , Mice , Mice, SCID , Neoplasm Transplantation , Neoplasms, Experimental/immunology , Thymus Gland/transplantation , Transplantation, HeterologousABSTRACT
Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited disease associated with germ-line mutations in mismatch repair genes and microsatellite instability. This article reviews the molecular biology and clinical pathology of HNPCC.
