With the exception of a few malignancies seemingly driven by a limited number of genetic lesions, current targeted therapeutic approaches have shown only limited efficacy in advanced cancers. Consequently, more sophisticated strategies, such as identification of pathogenic 'driver' mutations and optimization of personalized therapies are needed.

Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial.

Many biological and clinical features of chronic myeloid leukemia make it as a paradigm of rational drug design in human cancer. Chronic myeloid leukemia was the first malignancy to be linked to a clear genetic anomaly, the Philadelphia chromosome and, at present, it is probably the best understood of all human malignancies. Studies of the disease pathology revealed that the molecular consequence of the Philadelphia translocation is a BCR-ABL chimeric gene, which encodes a constitutively active tyrosine kinase with wholesale range of biological activities. Animal models have validated the direct role of the BCR-ABL protein in malignant transformation and subsequent research confirmed that its enhanced tyrosine kinase activity is essential and sufficient for the leukemogenesis. The very existence of a single genetic abnormality, presented in essentially all patients with the disease, made it an effective target for molecularly designed therapeutic approaches for the disease. The advent of tyrosine kinase inhibitors, designed specifically to inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein, represents one of the major innovations in cancer therapy and may serve as a model for, how discoveries of disease pathogenesis may be translated into the development of successful targeted therapies in cancer medicine.

Some cancer patients manifest leukocytosis without overt inflammation. The production of granulocyte colony-stimulating factor (G-CSF) by the tumor itself is thought to be responsible for this paraneoplastc syndrome.1-3) At least 80 cases of G-CSF-producing tumors have been reported up to the present. Although many types of G-CSF-producing tumors such as carcinoma of the thyroid, 4, 5) kidney, 6) oral cavity, 7) bladder, 8) gallbladder, 9) stomach, 10) hepatoma 11) and melanoma 12) have been reported, carcinoma of the lung [13][14][15][16][17] is predominant. Large cell carcinoma is the overwhelmingly dominant histologic type in lung cancer. 18,19) However, there have been few reports confirming the establishment of a G-CSF-producing cell line; to our knowledge, 10 G-CSF-producing lung cancer cell lines have been reported. Four of them are derived from large cell carcinoma. 14,[20][21][22] Recently, we studied a patient with large cell lung carcinoma who exhibited leukocytosis, and we established a new cell line in vitro from this patient. This cell line produces a high level of G-CSF in the medium. In this paper, we describe the establishment and characterization of this new lung cancer cell line. MATERIALS AND METHODS PatientThe patient was a 69-year-old male with large cell carcinoma of the lung. He underwent left upper lobectomy. Histologically, the surgical specimen of the lung tumor showed large cell undifferentiated carcinoma. However, the tumor metastasized to Virchow's node after 4 years. Chemotherapy and radiotherapy afforded only temporary control and the tumor grew rapidly. As the disease progressed, his peripheral blood white blood cell (WBC) count increased to 92 000/mm 3 with 95% mature neutrophils, without evidence of infection. The serum level of G-CSF was 141 pg/ml (normal <30 pg/ml). The patient gradually deteriorated with cachexia, and died 9 months after recurrence. At autopsy, metastatic tumors were found in the bilateral lungs, anterior mediastinum, right adrenal gland and retroperitoneal lymphnodes, besides Virchow's node. Furthermore, he had a large quantity of malignant pleural effusion and ascites. Cell culture Tumor cells were obtained from the pleural effusion and cultured for the establishment of a cell line.

Objective: To characterize the frequency of genetic profiles in pediatric acute lymphoblastic leukemia (ALL) patients in Kuwait. Subjects and Methods: This review presents the general cytogenetic characteristics of 164 pediatric patients diagnosed as having ALL in a 6-year period. Chromosomal and fluorescence in situ hybridization studies were made on bone marrow aspirates at diagnosis and during different stages of the disease. Results: Recurring aberrations, observed in 123 (75%) patients, included hyperdiploidy (n = 68, 41%), tetraploidy (n = 12, 7.3%), hypodiploidy (n = 2, 1.2%), TEL-AML1 fusion (n = 11, 7%), mixed-lineage leukemia rearrangement (n = 6, 3.6%), t(9;22) (n = 4, 2.4%), t(1;19) (n = 3, 1.8%), t(8;14) or t(8;22) (n = 2, 1.2%), +21 (n = 2, 1.2%), del(6) (n = 2, 1.2%) and miscellaneous abnormalities (n = 9, 5%). The highest observed numerical chromosome abnormality was high hyperdiploidy in 89 patients (54%) with abnormal karyotype while the TEL-AML fusion was the highest observed structural abnormality. Conclusion: This study showed that clonal anomalies detected in pediatric ALL have shown correlations between specific abnormalities and clinicobiological characteristics of the patients.