Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.

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Cancer Genome Landscapes

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.

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The cancer genome atlas pan-cancer analysis project

The Cancer Genome Atlas Pan-Cancer analysis project

Background Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non–small-cell lung cancers, representing 2 to 7% of such tumors. We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase. Methods After screening tumor samples from approximately 1500 patients with non–small-cell lung cancer for the presence of ALK rearrangements, we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial. Most of the patients had received previous treatment. These patients were enrolled in an expanded cohort study instituted after phase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles. Patients were assessed for adverse events and response to therapy. Results Patients with ALK rearrangements tended to be younger than those without the rearrangements, and most of the patients had little or no exposure to tobacco and had adenocarcinomas. At a mean treatment duration of 6.4 months, the overall response rate was 57% (47 of 82 patients, with 46 confirmed partial responses and 1 confirmed complete response); 27 patients (33%) had stable disease. A total of 63 of 82 patients (77%) were continuing to receive crizotinib at the time of data cutoff, and the estimated probability of 6-month progression-free survival was 72%, with no median for the study reached. The drug resulted in grade 1 or 2 (mild) gastrointestinal side effects. Conclusions The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.)

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Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer

https://www.hal.inserm.fr/inserm-00561753/document

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

The use of granulocyte colony stimulating factor (G-CSF) for recovery from neutropenia has been established; however, acute lung injury due to G-CSF-induced polymorphonuclear leukocyte (PMN) activa...

Continuous subcutaneous injection reduces polymorphonuclear leukocyte activation by granulocyte colony-stimulating factor.

Background The prognosis of lung cancer patients with intrapulmonary metastasis in different lobes (pm2) is poor. However, some patients achieve long-term survival. We retrospectively investigated the prognosis of resected primary lung cancer patients with pm2. Method Among 845 patients with primary lung cancer who underwent complete resection from 1984 to 2003, 14 cases that had lung cancer with pm2 were evaluated about prognostic factors. Results The overall 5-year survival rate was 9.5%. The analysis of survival curve based on clinicopathological factors (surgical procedure, histology, tumor size, lymph nodal metastasis, pleural invasion, pleural dissemination and number of pm2) revealed that bronchioloalveolar carcinoma (BAC), the absence of pleural invasion and the absence of pleural dissemination are better prognostic factors. Conclusion Lung cancer patients with pm2 whose lesions show BAC histology, the absence of pleural invasion or pleural dissemination may achieve long-term survival and could be candidates for surgical treatment.

Prognosis of patients after resection for lung cancer with intrapulmonary metastasis in different lobes

Leukocytes with bright fluorescence in rats.

学童期, 胸壁より侵入した肺内異物 (箸) により大量喀血した症例を経験したので報告した症例は20歳女性大量喀血が持続したため当院紹介入院となった胸部X線・CTで, 内容物を伴う空洞性病変を認め, 結核の既往歴のあることから, 出血性肺アスペルギルス症と診断した病巣へ流入する動脈塞栓術を行った後, 左上区域切除術を施行した術後標本では炎症性の空洞病変がありその内部に胸壁より侵入したと思われる肺内異物 (箸) が認められた経過良好で術後第11日に退院となった10年以上経過し, 喀血にて発症し, 画像上菌球様の病変を呈した経胸壁性異物について文献的考察を加え報告した

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Pulmonary foreign body (chopstick fragment) causing massive hemoptysis ; a case report

Two cases of spontaneous pneumothorax in the patients of Marfan Syndrome were reported. Nine and 13-year-old girls were admitted to our hospital complaining of chest pain and dyspnea for the first time. Tension pneumothorax was confirmed by the chest radiograph. Both of them had the physical stigmata of Marfan Syndrome including cardiovascular abnormalities. The drainage tube was inserted into the thoracic cavity. As the drainage was ineffective, the surgical treatment was undertaken. The thoracic cavity was opened though axillary incision and bullae were resected. The patient of pneumothorax with the Marfan Syndrome should be examined preoperatively about cardiovascular abnormality using chest computed tomography and echocardiography. As far as the surgical intervention was concerned, the axillary approach is preferred to the median sternotomy, as such patient highly probably require cardiovascular operation in future.

Yasunori Sohara

Papers

Continuous subcutaneous injection reduces polymorphonuclear leukocyte activation by granulocyte colony-stimulating factor.

Prognosis of patients after resection for lung cancer with intrapulmonary metastasis in different lobes

Leukocytes with bright fluorescence in rats.

Pulmonary foreign body (chopstick fragment) causing massive hemoptysis ; a case report

[Two cases of Marfan syndrome, surgically treated for complicating spontaneous pneumothorax].