We report a 53-year-old man with cancer of an unknown primary site with an epidermal growth factor receptor mutation for which gefitinib was effective. In 2007, he complained of left gluteal pain and right cervical lymph node swelling. He was given a diagnosis of adenocarcinoma at the biopsy of the right cervical lymph node. Although metastases of multiple lymph nodes, bone, and bilateral adrenal glands were found, the primary site could not be determined on close examination, resulting in a diagnosis of cancer of unknown primary site(poor prognosis group). He was then treated with systemic chemotherapy. After he showed resistance to chemotherapy, he received gefitinib as third-line therapy because the tumor harbored an epidermal growth factor receptor(EGFR)mutation. Subsequently, multiple metastatic tumors gradually reduced and clinical benefit was observed for a long time.

A 76-year-old man with renal dysfunction received FOLFIRI due to a relapse in his pelvis after surgery for sigmoid colon cancer. FOLFIRI was continued for approximately 21 months with stabilization of disease observed on CT scans, but his tumor marker levels increased and tumors showed progression. He then began treatment with cetuximab/CPT-11, but disease progression was observed. XELOX in a low-dose was then administered, but this therapy was discontinued because of progression. He could not receive the other antitumor agents, due to mutations of the KRAS gene and renal dysfunction. Therefore, FOLFIRI was restarted, because it can be continued for long periods of time. Consequently, his tumor marker levels decreased with stabilization of disease on CT scans, and he continued the therapy for 7 months while maintaining quality of life. Ultimately, this case suggested that if there was effectiveness from a previous treatment, retreatment would be successful as chemotherapy for colon cancer in the difficult situation of selecting the other effective antitumor agents.

Cetuximab is a recombinant, human/mouse chimeric monoclonal antibody that binds specifically to the extracellular domain of the human epidermal growth factor receptor(EGFR). This targeting agent was permitted for use with unresectable colorectal cancer patients whose tumor tissue express positive EGFR immunohistochemical staining in Japan from September 2008. Cetuximab was certified its beneficial response to KRAS wild-type patients while EGFR expression was not a proof of response. That, however, is not the only predictive factor, but skin toxicity as an adverse event is considered to be a good predictive factor. We retrospectively evaluated skin toxicity to determine whether or not its appearance would be the predictive factor of cetuximab response to 66 colorectal cancer patients in our institution. The result should that 93. 8% of patients who experienced severe skin toxity(grade 2-3)responded well(SD, PR and CR)to cetuximab.

The fourth edition of the "WHO Classification of Tumours of Haematopoietic and Lymphoid tissues" was published in 2008 as an updated version of the third edition published in 2001. In this review, the revised points in the lymphoid neoplasms in the fourth edition were summarized from the viewpoint of doctors and medical technologists in clinical laboratories in hospitals. The diseases are classified based on information about morphology, immunophenotype, genetic features, and clinical features. B lymphoblastic leukemia/lymphoma with 7 recurrent genetic abnormalities is individually classified as a provisional entity. Anaplastic large cell lymphoma is divided into two entities, ALK positive and ALK-negative. The pathogenesis of the former is involved with ALK gene rearrangement with several partner genes. Two borderline categories between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, and between DLBCL and classical Hodgkin lymphoma are newly recognized as a distinct disease entity based on the overlapping morphological and genetic features. In the diagnosis of lymphoid neoplasms, understanding the morphological features is fundamental. On the other hand, the importance of immunohistochemistry and flow cytometry to clarify the immunophenotype, and chromosomal analysis and genetic examination to clarify the genetic features has been raised.

The Fas-associated death domain containing protein, FADD, is an adaptor for relaying apoptotic signals. However, recent studies have shown that FADD also plays an important role in the growth and regulation of the cell cycle, and FADD gene amplifications were observed in oral squamous cell carcinoma (OSCC). The purpose of this study was to elucidate the role of FADD in oral leukoplakia, known as potentially malignant disorder.

A 63-year-old female with BJP-multiple myeloma (Durie-Salmon stage III B, International Staging System III) showed an increased level of KL-6, a sialylated carbohydrate antigen that is a MUC1 molecule expressed in type II pneumocytes and reflects activity of interstitial pneumonia. At the time of diagnosis, KL-6 was as high as 22,030 U/ml; however, surfactant protein D (SP-D) was normal, and stroma-related pneumonia was not indicated on CT images. Expression of KL-6 in multiple myeloma cells was detected by immunostaining and the patient was diagnosed with KL-6-positive multiple myeloma. Usually, MUC1 is encoded by chromosome 1q21, but the karyotypic analysis of the patient's bone marrow cells lacked chromosome 1. KL-6 increased as the disease progressed. The patient did not respond to chemotherapy, including bortezomib, showed an increase of pleural effusion, and died. For this patient, multiple myeloma with high KL-6 was refractory to chemotherapy, suggesting that new treatment strategies, including transplantation of hematopoietic stem cells, are required.

Somatic activating mutations in the epidermal growth factor receptor (EGFR) gene were first identified in 2004 from tumor tissues of non-small cell lung cancer (NSCLC) patients and pulmonary adenocarcinoma cell lines. Although pulmonary adenocarcinoma patients harboring EGFR mutations have increased sensitivity to EGFR tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, the primary and acquired resistant cases remain major clinical problems. Therapeutic strategies for such oncogene-driven carcinomas were intensively investigated at both the clinical and preclinical levels. In this review, we focused on one particular molecularly-defined subset of NSCLC that harbors activating mutations in the EGFR gene. We summarized the rational dissection of the mechanisms of drug sensitivity and resistance to EGFR-TKIs, and the promising molecular-centric strategies for further improving the outcomes of NSCLC patients with EGFR activating mutations.

Translocation (8;21)/AML1-ETO is considered a favorable cytogenetic abnormality in acute myeloid leukemia (AML). However, the outcomes associated with KIT mutations in AML1-ETO have not been elucidated. A 16-year-old boy was diagnosed with recurrent AML. Although he underwent hematopoietic stem cell transplantation (HSCT) twice, the leukemia relapsed and grew resistant to several chemotherapies. We began to treat him with imatinib, but stopped on the 31st day as it did not show any effects. Later, we administered dasatinib. However, we discontinued this because he showed severe nasal hemorrhage 87 days after administration of dasatinib. The therapeutic benefit of tyrosine-kinase inhibitor (TKI) was estimated by quantitative analysis of AML1-ETO and the patient's clinical impression. We did not conduct analyses to determine the effective concentration of TKI. The patient has not yet shown any major molecular response. Therefore, we conclude that TKI may be useful for slight palliation of symptoms in KIT-positive AML. However, patients with refractory AML associated KIT mutations in AML1-ETO should not be considered for TKI monotherapy.

The most effective drugs based on the type of cancer are chosen for chemotherapy. Tumor cells can be targeted at the DNA, RNA or protein level, and most of the classical anticancer drugs interact with tumor DNA in a time-dependent manner or a concentration-dependent manner. However, it has been unclear to date whether a combination therapy is carried out by using exact classification. Thus it is necessary to reclassify a great number of anticancer drugs. We propose a new classification system based on pharmacological effects of anticancer drugs. Classification of four anticancer drugs (cisplatin, carboplatin, paclitaxel and gemcitabine) was performed by the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The four anticancer drugs were grouped by IC50 values (inhibitory concentration, 50%) in a time-dependent manner and a concentration-dependent manner. The present approach may be combined to enhance the chemosensitivity, improve the dose of cytotoxic drugs and evaluate the effects of novel anticancer drugs.

β-1,4-Galactosyltransferase (β-1,4-GalT) V - whose human and mouse genes were cloned by us - has been suggested to be involved in the biosyntheses of N-glycans, O-glycans, and lactosylceramide by in vitro studies. Our recent study showed that β-1,4-GalT V-knockout mice are embryonic lethal, suggesting the importance of the glycans synthesized by β-1,4-GalT V for embryonic development. A subsequent study showed that murine β-1,4-GalT V is involved in the biosynthesis of lactosylceramide. It is well known that the glycosylation of cell surface glycoproteins and glycolipids changes dramatically upon the malignant transformation of cells. We found that among six β-1,4-GalTs the gene expression of only β-1,4-GalT V increases upon malignant transformation. The expression of the β-1,4-GalT V gene has been shown to be regulated by transcription factors Sp1 and Ets-1 in cancer cells. Both transcription factors regulate the gene expression levels of not only glycosyltransferases, but also key molecules involved in tumor growth, invasion and metastasis. Therefore, the abnormal glycosylation and malignant phenotypes of cancer cells are considered to be suppressed by regulating the expression levels of the transcription factor genes. This review gives a summary account of the gene discovery, in vivo function, and transcriptional mechanism of β-1,4-GalT V. Also, a perspective on applications of the manipulation of transcription factor genes to cancer therapy will be discussed.