[A Case of Breast Cancer That Developed Pulmonary Tumor Thrombotic Microangiopathy during Adjuvant Chemotherapy].

A 68-year-old woman underwent neoadjuvant chemotherapy for left breast cancer(triple negative type), cT2N3cM0, cStage ⅢC, and Bt+Ax(Ⅲ). The pathological diagnosis was ypT1aN2aM0, ypStage ⅢA, ER-, PgR-, HER2 score 1+, Ki- 67 25%. Adjuvant radiotherapy(50 Gy/25 Fr)was then administered, followed by capecitabine as adjuvant chemotherapy. Dyspnea occurred during administration of capecitabine, and computed tomography(CT)and blood test results suggested drug-induced interstitial pneumonia and disseminated intravascular coagulation(DIC). The patient was admitted, and steroid pulse therapy, anticoagulant therapy, and antibiotics were administered; however, the treatment was ineffective, and she died 3 days after admission. An autopsy provided a final diagnosis of pulmonary tumor thrombotic microangiopathy(PTTM). There is no established treatment for PTTM, and the prognosis is poor even with anticoagulant therapy and chemotherapy. The definitive diagnosis of PTTM is based on pathological findings; however, during respiratory failure, invasive tests such as lung biopsy are not recommended. Therefore, if a significantly worsening respiratory disorder develops, as in this case, chemotherapy should be considered for suspected PTTM.

A large iliopsoas abscess due to colon cancer complicated by bowel obstruction: A case report.

INTRODUCTION: Iliopsoas abscesses (IPAs) associated with bowel obstruction due to colon cancer are rare, and there is no consensus regarding treatment strategies. PRESENTATION OF CASE: A 63-year-old man presented with swelling and pain in the right iliac region. Imaging studies revealed an IPA expanding from the psoas major muscle and retroperitoneal space subcutaneously around the right ilium. After percutaneous drainage, the patient developed bowel obstruction secondary to colon cancer. Hemicolectomy and preventive ileostomy were performed at the gastrointestinal surgery department, and chemotherapy was administered at the medical oncology department after ileostomy closure. Three months later, local recurrence was confirmed in the right iliac region, and the recurrent lesion, including the ilium, was widely resected. One and a half years after the reoperation, there was no recurrence. DISCUSSION: An IPA due to colorectal cancer without obvious perforation can also occur, and the treatment of IPAs depends on their size, location, shape, and presence of gas. Minimally invasive and staged treatment is preferable for IPAs due to colorectal cancer because the surgical mortality rate for colorectal cancer with local abscesses is high. CONCLUSION: Colorectal cancer should be considered as a cause of IPAs. Treatment of IPAs caused by colon cancer should be performed in a less invasive manner after considering their size, location, shape, and the presence of gas. Cooperation between gastrointestinal surgeons and oncologists is essential for managing patients with an IPA due to colon cancer complicated by bowel obstruction.

FANCD2 protects genome stability by recruiting RNA processing enzymes to resolve R-loops during mild replication stress.

R-loops, which consist of DNA : RNA hybrids and displaced single-strand DNA, are a major threat to genome stability. We have previously reported that a key Fanconi anemia protein, FANCD2, accumulates on large fragile genes during mild replication stress in a manner depending on R-loops. In this study, we found that FANCD2 suppresses R-loop levels. Furthermore, we identified FANCD2 interactions with RNA processing factors, including hnRNP U and DDX47. Our data suggest that FANCD2, which accumulates with R-loops in chromatin, recruits these factors and thereby promotes efficient processing of long RNA transcripts. This may lead to a reduction in transcription-replication collisions, as detected by PLA between PCNA and RNA Polymerase II, and hence, lowered R-loop levels. We propose that this mechanism might contribute to maintenance of genome stability during mild replication stress.

FANCD2 binds CtIP and regulates DNA-end resection during DNA interstrand crosslink repair.

The Fanconi anemia (FA) pathway is critically involved in the maintenance of hematopoietic stem cells and the suppression of carcinogenesis. A key FA protein, FANCD2, is monoubiquitinated and accumulates in chromatin in response to DNA interstrand crosslinks (ICLs), where it coordinates DNA repair through mechanisms that are still poorly understood. Here, we report that CtIP protein directly interacts with FANCD2. A region spanning amino acids 166 to 273 of CtIP and monoubiquitination of FANCD2 are both essential for the FANCD2-CtIP interaction and mitomycin C (MMC)-induced CtIP foci. Remarkably, both FANCD2 and CtIP are critical for MMC-induced RPA2 hyperphosphorylation, an event that accompanies end resection of double-strand breaks. Collectively, our results reveal a role of monoubiquitinated FANCD2 in end resection that depends on its binding to CtIP during ICL repair.

A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair.

When DNA replication is stalled at sites of DNA damage, a cascade of responses is activated in the cell to halt cell cycle progression and promote DNA repair. A pathway initiated by the kinase Ataxia teleangiectasia and Rad3 related (ATR) and its partner ATR interacting protein (ATRIP) plays an important role in this response. The Fanconi anemia (FA) pathway is also activated following genomic stress, and defects in this pathway cause a cancer-prone hematologic disorder in humans. Little is known about how these two pathways are coordinated. We report here that following cellular exposure to DNA cross-linking damage, the FA core complex enhances binding and localization of ATRIP within damaged chromatin. In cells lacking the core complex, ATR-mediated phosphorylation of two functional response targets, ATRIP and FANCI, is defective. We also provide evidence that the canonical ATR activation pathway involving RAD17 and TOPBP1 is largely dispensable for the FA pathway activation. Indeed DT40 mutant cells lacking both RAD17 and FANCD2 were synergistically more sensitive to cisplatin compared with either single mutant. Collectively, these data reveal new aspects of the interplay between regulation of ATR-ATRIP kinase and activation of the FA pathway.