Interstitial lung disease associated with adjuvant and neoadjuvant chemotherapy in early breast cancer.

BACKGROUND: Interstitial lung disease (ILD) is a rare adverse event in patients receiving adjuvant or neoadjuvant chemotherapy (NAC) for breast cancer. Few studies have reported the frequency of ILD in detail, and only small numbers of cases have been described in the literature. Given these previous findings concerning ILD, we retrospectively examined the clinicopathological characteristics of five cases of ILD who had received epirubicin and cyclophosphamide (EC) and compared their findings with non-ILD cases. METHODS: The present single-center retrospective study included breast cancer patients who underwent adjuvant chemotherapy or NAC at our hospital between January 2014 and January 2021. RESULTS: Thirty-nine patients who had received EC for operable breast cancer were enrolled in this study. ILD developed 5 out of 39 patients (12.8%). The incidence of ILD in patients with non-dose-dense (dd) or dd chemotherapy was statistically significantly different (p = 0.0149). ILD occurred in three patients during dd EC treatment and two during weekly paclitaxel (wPTX) after dd EC. ILD was detected in one patient with high Krebs von den Lungen-6 (KL-6) levels, in two patients with continuous pyrexia, and in two patients from computed tomography imaging, which was taken to estimate the efficacy of chemotherapy, in two patients. Three of the 5 ILD patients underwent bronchoalveolar lavage, and 2 of these patients were diagnosed with Pneumocystis jirovecii pneumonia (PCP). There were no cases of serious ILD that required steroid pulse therapy. CONCLUSIONS: Dd chemotherapy may be associated with an increased ILD frequency, which may reflect developing PCP. Careful monitoring and a timely diagnosis are useful for detecting early-stage ILD.

A systematic review of observational studies of trifluridine/tipiracil (TAS-102) for metastatic colorectal cancer.

Background: The treatment options for patients with therapy refractory metastatic colorectal cancer (mCRC) are sparse. TAS-102 (FTD/TPI) is a new oral anti-tumour agent composed of a nucleoside analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil, indicated for patients with mCRC who are refractory to standard therapies. This study summarizes published and unpublished experience with FTD/TPI in clinical practice settings. Patients and methods: The Medline/PubMed, Embase and Cochrane Library databases were searched to identify observational studies on FTD/TPI monotherapy for mCRC. Papers describing use of FTD/TPI monotherapy outside clinical trials in series of patients evaluable for effectiveness were eligible. The outcomes of interest were median progression free survival (mPFS), median overall survival (mOS) as well as mean PFS time restricted to six months (PFS6m) and mean OS time restricted to one year (OS1y). Results of the pooled analyses of observational studies were compared to the results of the Japanese phase II trial and the two phase III trials, RECOURSE and TERRA. Results: Seven published and two unpublished studies with 1008 patients from 64 centres were included for analysis. The pooled mPFS was 2.2 months (95% CI 2.1 to 2.3 months), and the pooled mOS was 6.6 months (95% CI 6.1 to 7.1 months). PFS6m was 2.9 months (95% CI 2.6 to 3.1 months) and OS1y was 6.8 (95% CI 6.0 to 7.5) months. While these results all reflect RECOURSE, the pooled mOS is lower than in the phase II trial and the OS1y is inferior to both the phase II trial and TERRA. Conclusion: This systematic review and a meta-analysis indicates that in real life settings, the survival benefit of FTD/TPI monotherapy in patients with therapy refractory mCRC reflects the outcomes in RECOURSE but is inferior to outcomes in the two Asian efficacy trials. What is already known TAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic colorectal cancer (mCRC). A Japanese phase II trial and two phase III trials, RECOURSE and TERRA, demonstrated that FTD/TPI prolonged overall survival. What this study adds This systematic review and meta-analysis of real life data from 64 sites indicates that the effectiveness in daily clinical practice settings of FTD/TPI monotherapy in late stage mCRC reflects the outcomes in RECOURCE but is inferior to the outcomes in the Japanese phase II trial and TERRA.

Use of hormone therapies in disseminated carcinomatosis of the bone marrow associated with hormone receptor-positive breast cancer.

Disseminated carcinomatosis of the bone marrow (DCBM) is diffusely invasive bone metastasis resulting from solid tumors. DCBM is often associated with disseminated intravascular coagulation (DIC) or hemolytic anemia. Generally, DCBM treatment includes cytotoxic chemotherapy for underlying solid tumors and management of hematological conditions if present. We report a case of DCBM accompanied with DIC in hormone receptor-positive breast cancer. Due to her life-threatening condition, we used hormone therapies, not cytotoxic chemotherapies, to treat her DCBM. With zoledronic acid, her DIC and general condition gradually improved and eventually she could return to her daily life. If DCBM occurs in hormone receptor-positive breast cancer, hormone therapy can be one of the treatment choices.

TP53 mutations, tetraploidy and homologous recombination repair defects in early stage high-grade serous ovarian cancer.

To determine early somatic changes in high-grade serous ovarian cancer (HGSOC), we performed whole genome sequencing on a rare collection of 16 low stage HGSOCs. The majority showed extensive structural alterations (one had an ultramutated profile), exhibited high levels of p53 immunoreactivity, and harboured a TP53 mutation, deletion or inactivation. BRCA1 and BRCA2 mutations were observed in two tumors, with nine showing evidence of a homologous recombination (HR) defect. Combined Analysis with The Cancer Genome Atlas (TCGA) indicated that low and late stage HGSOCs have similar mutation and copy number profiles. We also found evidence that deleterious TP53 mutations are the earliest events, followed by deletions or loss of heterozygosity (LOH) of chromosomes carrying TP53, BRCA1 or BRCA2. Inactivation of HR appears to be an early event, as 62.5% of tumours showed a LOH pattern suggestive of HR defects. Three tumours with the highest ploidy had little genome-wide LOH, yet one of these had a homozygous somatic frame-shift BRCA2 mutation, suggesting that some carcinomas begin as tetraploid then descend into diploidy accompanied by genome-wide LOH. Lastly, we found evidence that structural variants (SV) cluster in HGSOC, but are absent in one ultramutated tumor, providing insights into the pathogenesis of low stage HGSOC.

Network-based survival analysis reveals subnetwork signatures for predicting outcomes of ovarian cancer treatment.

Cox regression is commonly used to predict the outcome by the time to an event of interest and in addition, identify relevant features for survival analysis in cancer genomics. Due to the high-dimensionality of high-throughput genomic data, existing Cox models trained on any particular dataset usually generalize poorly to other independent datasets. In this paper, we propose a network-based Cox regression model called Net-Cox and applied Net-Cox for a large-scale survival analysis across multiple ovarian cancer datasets. Net-Cox integrates gene network information into the Cox's proportional hazard model to explore the co-expression or functional relation among high-dimensional gene expression features in the gene network. Net-Cox was applied to analyze three independent gene expression datasets including the TCGA ovarian cancer dataset and two other public ovarian cancer datasets. Net-Cox with the network information from gene co-expression or functional relations identified highly consistent signature genes across the three datasets, and because of the better generalization across the datasets, Net-Cox also consistently improved the accuracy of survival prediction over the Cox models regularized by L(2) or L(1). This study focused on analyzing the death and recurrence outcomes in the treatment of ovarian carcinoma to identify signature genes that can more reliably predict the events. The signature genes comprise dense protein-protein interaction subnetworks, enriched by extracellular matrix receptors and modulators or by nuclear signaling components downstream of extracellular signal-regulated kinases. In the laboratory validation of the signature genes, a tumor array experiment by protein staining on an independent patient cohort from Mayo Clinic showed that the protein expression of the signature gene FBN1 is a biomarker significantly associated with the early recurrence after 12 months of the treatment in the ovarian cancer patients who are initially sensitive to chemotherapy. Net-Cox toolbox is available at http://compbio.cs.umn.edu/Net-Cox/.

Soluble immune checkpoint factors reflect exhaustion of antitumor immunity and response to PD-1 blockade.

BACKGROUNDPrecise stratification of patients with non-small cell lung cancer (NSCLC) is needed for appropriate application of PD-1/PD-L1 blockade therapy.METHODSWe measured soluble forms of the immune-checkpoint molecules PD-L1, PD-1, and CTLA-4 in plasma of patients with advanced NSCLC before PD-1/PD-L1 blockade. A prospective biomarker-finding trial (cohort A) included 50 previously treated patients who received nivolumab. A retrospective observational study was performed for patients treated with any PD-1/PD-L1 blockade therapy (cohorts B and C), cytotoxic chemotherapy (cohort D), or targeted therapy (cohort E). Plasma samples from all patients were assayed for soluble immune-checkpoint molecules with a highly sensitive chemiluminescence-based assay.RESULTSNonresponsiveness to PD-1/PD-L1 blockade therapy was associated with higher concentrations of these soluble immune factors among patients with immune-reactive (hot) tumors. Such an association was not apparent for patients treated with cytotoxic chemotherapy or targeted therapy. Integrative analysis of tumor size, PD-L1 expression in tumor tissue (tPD-L1), and gene expression in tumor tissue and peripheral CD8+ T cells revealed that high concentrations of the 3 soluble immune factors were associated with hyper or terminal exhaustion of antitumor immunity. The combination of soluble PD-L1 (sPD-L1) and sCTLA-4 efficiently discriminated responsiveness to PD-1/PD-L1 blockade among patients with immune-reactive tumors.CONCLUSIONCombinations of soluble immune factors might be able to identify patients unlikely to respond to PD-1/PD-L1 blockade as a result of terminal exhaustion of antitumor immunity. Our data suggest that such a combination better predicts, along with tPD-L1, for the response of patients with NSCLC.TRIAL REGISTRATIONUMIN000019674.FUNDINGThis study was funded by Ono Pharmaceutical Co. Ltd. and Sysmex Corporation.

Long-term survival with nivolumab followed by irinotecan after total gastrectomy in alpha-fetoprotein-producing gastric cancer: a case report and review of the literature.

BACKGROUND: Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare type of aggressive gastric cancer (GC) with a dismal prognosis. We present a patient with AFPGC who achieved long-term survival through a multidisciplinary approach. CASE PRESENTATION: A 67-year-old man with advanced GC was referred to our hospital for systemic chemotherapy. He was diagnosed with cStage IVB AFPGC. During 2nd-line treatment, we could not control bleeding from the GC itself. After complete resection, during chemotherapy, portal venous tumor thrombi (PVTTs) and liver metastases were identified. With nivolumab followed by irinotecan, the PVTTs and liver metastases disappeared. Without immunotherapy and chemotherapy for 23 months, the patient has survived for 48 months so far with no recurrence of GC. CONCLUSION: Long-term survival with AFPGC can be accomplished by using several different approaches, such as surgery, immunotherapy, and chemotherapy.

Comprehensive Kinase Activity Profiling Revealed the Kinase Activity Patterns Associated with the Effects of EGFR Tyrosine Kinase Inhibitor Therapy in Advanced Non-Small-Cell Lung Cancer Patients with Sensitizing EGFR Mutations.

EGFR mutations are strong predictive markers for EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in patients with non-small-cell lung cancer (NSCLC). Although NSCLC patients with sensitizing EGFR mutations have better prognoses, some patients exhibit worse prognoses. We hypothesized that various activities of kinases could be potential predictive biomarkers for EGFR-TKI treatment among NSCLC patients with sensitizing EGFR mutations. In 18 patients with stage IV NSCLC, EGFR mutations were detected and comprehensive kinase activity profiling was performed using the peptide array PamStation12 for 100 tyrosine kinases. Prognoses were observed prospectively after the administration of EGFR-TKIs. Finally, the kinase profiles were analyzed in combination with the prognoses of the patients. Comprehensive kinase activity analysis identified specific kinase features, consisting of 102 peptides and 35 kinases, in NSCLC patients with sensitizing EGFR mutations. Network analysis revealed seven highly phosphorylated kinases: CTNNB1, CRK, EGFR, ERBB2, PIK3R1, PLCG1, and PTPN11. Pathway analysis and Reactome analysis revealed that the PI3K-AKT and RAF/ MAPK pathways were significantly enriched in the poor prognosis group, being consistent with the outcome of the network analysis. Patients with poor prognoses exhibited high activation of EGFR, PIK3R1, and ERBB2. Comprehensive kinase activity profiles may provide predictive biomarker candidates for screening patients with advanced NSCLC harboring sensitizing EGFR mutations.

Disappearance of recurrent thymic epithelial tumor following corticosteroid and cyclosporine treatment: A case report.

Thymic epithelial tumors (TETs) are considered orphan neoplasms, and treatment options for recurrent or metastatic stages are limited. Here, we have reported a case of recurrent TET that showed complete remission after receiving high-dose corticosteroids followed by low-dose corticosteroids and cyclosporine. No recurrence was observed for the next 2 years. The effects of corticosteroids on the TET and the associated pure red cell aplasia led to adjustment of the diagnosis from thymic carcinoma to thymoma. Low-dose corticosteroids and cyclosporine might be the reason for remission maintenance.

Minichromosome maintenance protein 7 as a potential prognostic factor for progression-free survival in high-grade serous carcinomas of the ovary.

Minichromosome maintenance protein 7 (MCM7) is involved in replicative licensing and synthesis of DNA. It was previously identified as an overexpressed gene in high-grade serous carcinomas compared with serous borderline tumors of the ovary in cDNA microarray studies. In this study, we sought to validate MCM7 expression in 342 ovarian tumors on tissue microarrays. MCM7 expression was quantified as the MCM7 labeling index, and it was independently generated by two methods: a score provided by manual review of each sample by a pathologist observer and by an automated cellular imaging system. Analyses of MCM7 scores indicated a high degree of concordance and distribution between the observer- and machine-generated MCM7 labeling indexes. MCM7 expression was significantly higher in high-grade serous carcinomas than in serous borderline tumors or other histological subtypes of ovarian cancer. For both observer- and machine-derived scores, univariate analyses indicated the significant association of a high MCM7 labeling index with better progression-free survival in high-grade serous carcinomas. These results suggest the clinical importance of MCM7 expression in high-grade serous carcinomas of the ovary and the need for further evaluation of MCM7 as a potential prognostic factor in ovarian cancer.

Rapid and dramatic responses to dabrafenib and trametinib in BRAF V600E-mutated lung adenocarcinoma.

V-raf murine sarcoma viral oncogene homologue B1 (BRAF) is a proto-oncogene that regulates cell proliferation and survival. BRAF V600E-mutated lung cancer has aggressive characteristics and is resistant to chemotherapies. Combination of BRAF-specific inhibitor dabrafenib and mitogen-activated protein kinase kinase (MEK) inhibitor trametinib is the standard treatment for BRAF V600E-mutated lung cancer. We report a case of BRAF V600E-mutated lung adenocarcinoma, which presented with respiratory distress due to deterioration of advanced cancer. The tumour responded rapidly and significantly to BRAF/MEK inhibitors, and the patient's symptoms improved within 2 weeks. BRAF/MEK inhibitors are effective treatment in BRAF-mutated lung cancer even under critical conditions.

Expression and function of HOXA genes in normal and neoplastic ovarian epithelial cells.

We studied the roles of three HOXA genes in cultured normal ovarian surface epithelial (OSE) cells and ovarian cancer cells. They included HOXA4 and HOXA7 because, by cDNA microarray analysis, these were more highly expressed in invasive ovarian carcinomas than in benign or borderline (noninvasive) ovarian tumors, and HOXA9 because it characterizes normal oviductal epithelium, which resembles ovarian serous adenocarcinomas. The three HOXA genes were more highly expressed when OSE cells were dividing and motile than when they were confluent and stationary, and also when they dispersed in response to EGF treatment or to reduced calcium concentrations in culture media. The expression of the HOXA genes varied among ovarian cancer cell lines, but was highest in lines with compact epithelial morphologies. We focused on HOXA4 as the most highly expressed in the ovarian carcinoma array. HOXA4 expression did not parallel proliferative activities of either OSE or ovarian cancer lines. Moreover, modifying HOXA4 expression in ovarian cancer cell lines did not alter either E-cadherin expression or CA125 secretion. However, HOXA4 downregulation enhanced EGFR phosphorylation and migration in serum-starved OSE and ovarian cancer cells in response to EGF, and enhanced migration of all ovarian cancer lines in 5% serum even without EGF treatment. Thus, HOXA4 expression does not correlate with proliferation or with epithelial differentiation, but it increases in response to OSE cell dispersion and negatively regulates EGFR activation and the motility of OSE and of ovarian cancer cells. HOXA4 expression was highest in cancer lines with compact epithelial growth patterns, suggesting, again, an anti-dispersion function. In summary, increased HOXA4 expression in ovarian cancer appears to constitute a tumor-suppressive, homeostatic response to aberrant cell behavior, and, in particular, to cell dispersion and migration.

False-Positive Elevation of CK-MB Levels with Chest Pain in Lung Adenocarcinoma.

The creatinine kinase (CK)-MB assay can be used for the early diagnosis of acute coronary syndrome. We describe the case of an 82-year-old male with lung adenocarcinoma who presented with chest pain. While laboratory findings showed elevated CK-MB levels, there was no cardiac injury. A chest computed tomography scan revealed pleural carcinomatosis. Later, electrophoretic analysis of CK showed a normal CK-MB range but increased CK-BB levels and the presence of macro CK type 2. We determined that the patient's chest pain originated from the visceral pleural invasion of lung cancer. Because of the methods used to measure the CK-MB isozyme, the CK-MB level appeared elevated.

Serum immune modulators during the first cycle of anti-PD-1 antibody therapy in non-small cell lung cancer: Perforin as a biomarker.

BACKGROUND: Currently used biomarkers for immunotherapy are inadequate because they are only based on tumor properties. In view of microenvironment changes by tumors, host immunity should be considered, which may result in identifying more accurate and easily detectable biomarkers for daily clinical practice. Here, we assessed serum immune-modulating factor levels for the response to anti-PD-1 antibodies during the first cycle in non-small cell lung cancer (NSCLC) patients. METHODS: Serum was collected from patients with advanced NSCLC treated with nivolumab or pembrolizumab at several time points during the first cycle. We applied the enzyme-linked immunosorbent assays (ELISAs) and multiplex assays to measure the levels of immune modulators. RESULTS: A total of 40 patients treated with nivolumab and 26 patients treated with pembrolizumab were studied. By ELISA, serum perforin, but not granzyme B, was measured in all samples. By multiplex assay, 10 immune modulators, including granzyme B, were measured in some, but not all, samples. Serum baseline perforin levels were strongly associated with increased progression-free survival (PFS) and overall survival (OS) times. Sequential changes in perforin levels during the first cycle were weakly associated with the clinical outcome. CONCLUSIONS: Serum baseline perforin levels may be used to predict the prognosis of NSCLC patients treated with anti-PD-1 antibody therapy. KEY POINTS: To identify a useful predictive marker for anti-PD-1 antibody therapy, using blood samples might be helpful. Serum baseline perforin levels were closely associated with prognosis with anti-PD-1 antibody therapy in non-small cell lung cancer.

Analysis of gene expression in stage I serous tumors identifies critical pathways altered in ovarian cancer.

OBJECTIVE: Despite recent advances in the conceptual understanding of the pathogenesis of ovarian cancer, it remains the foremost cause of death from gynecologic malignancies in developed countries. The main reason for such a high rate of mortality is the lack of sensitive and specific biomarkers and imaging techniques for early detection of ovarian cancer. Additional biological insights into early-stage ovarian carcinogenesis are needed to help speed the development of markers for early detection of ovarian cancer. The objective of this study was to characterize differentially expressed genes in high-grade stage I serous carcinoma of the ovary. METHODS: We analyzed gene expression in macrodissected formalin-fixed, paraffin-embedded samples from 5 high-grade stage I serous carcinomas and 5 stage I borderline tumors of the ovary using the Illumina Whole Genome DASL assay (cDNA-mediated annealing, selection, extension, and ligation) corresponding to 24,000 genes. Significance Analysis of Microarrays was performed to determine differentially expressed genes in stage I serous carcinoma, and class prediction analysis was performed to determine the predictive value of differentially expressed gene sets to correctly classify serous carcinoma from borderline tumors in 3 independent data sets. Altered transcription factor pathways and biological pathways unique to stage I serous carcinoma were identified through class comparison of differentially expressed genes. RESULTS: Unsupervised cluster analysis of gene expression correctly classified stage I serous carcinomas from serous borderline tumors. Supervised analysis identified several known, as well as novel, genes differentially expressed in stage I ovarian cancer. Using a differentially expressed gene set, class comparison prediction analysis correctly identified serous carcinomas from serous borderline tumors in 3 independent data sets at over 80% accuracy, sensitivity, and specificity. Pathway analysis demonstrated the significance of p53 and E2F pathways in serous carcinogenesis and significant involvements of cell cycle and immune response pathways in stage I serous epithelial ovarian cancer. CONCLUSION: We have identified differentially expressed genes associated with the carcinogenesis of high-grade stage I serous EOC. Furthermore, integrative analysis of biological and transcription pathway data contributed to the confirmation of important biological pathways and discovery of additional unique genes and pathways that may have potential importance in ovarian pathogenesis and biomarker development.

Porous diaphragm syndrome with recurrent thymoma.

Porous diaphragm syndrome describes a defect in the diaphragm in which substances pass from the peritoneal cavity to the pleural space. Defects may be congenital or acquired. Acquired defects are caused by the thinning and eventual splitting of collagen fibres in the tendinous part of the diaphragm. We report a case of porous diaphragm syndrome with recurrent thymoma that presented with massive ascites. Increasing intra-abdominal pressure by ascites and diaphragmatic thinning due to malnutrition by malignancies resulted in the formation of an artificial hole. Thoracentesis changed the balance of hydrostatic pressure, which initiated the influx of a large volume of ascites to the pleural cavity through a hole in the diaphragm.

Successful Desensitization with Crizotinib after Crizotinib-induced Liver Injury in ROS1-rearranged Lung Adenocarcinoma.

Crizotinib has been approved for patients with advanced lung adenocarcinoma harboring rearrangements of the c-ROS-1 (ROS1) and anaplastic lymphoma kinase (ALK) genes. We report a patient with ROS1-rearranged lung adenocarcinoma who developed a crizotinib-induced mixed/cholestatic type of liver injury. The patient discontinued crizotinib after 34 days due to liver toxicity. Twenty-four days later, when transaminases and C reactive protein (CRP) were normalized, crizotinib was resumed using an oral desensitization method. The patient was successfully treated for manageable recurrence of liver injury and has been able to continue the treatment.

HOX cofactors expression and regulation in the human ovary.

BACKGROUND: HOX cofactors enhance HOX binding affinities and specificities and increase HOX's unique functional activities. The expression and the regulation of HOX cofactors in human ovaries are unknown. METHODS: In this study, the expression of HOX cofactors, PBX1, PBX2, and MEIS1/2, were examined by using RT-PCR, immunofluorescence in cultured immortalized human granulosa (SVOG) cells. The distribution of these HOX cofactors in human ovaries was examined by immunohistochemistry. The effects of growth differentiation factor-9 (GDF-9) and follicle-stimulating hormone (FSH) on PBX2 in SVOG cells were investigated by western blot analysis. Binding activities of HOXA7 and PBX2 to the specific sequences in granulosa cells were determined by electrophoretic mobility shift assay (EMSA). RESULTS AND CONCLUSION: In SVOG cells, PBX1, PBX2 and MEIS1/2 were expressed during cell culture. In normal human ovaries, PBX1 and MEIS1/2 were expressed in granulosa cells at essentially all stages of follicular development. These cofactors were expressed in the nuclei of the granulosa cells from the primordial to the secondary follicles, whereas beyond multilayered follicles was observed in the cytoplasm. The co-expression of PBX1 and MEIS1/2 in granulosa cells in normal human ovaries suggested that MEIS1/2 might control PBX1 sublocalization, as seen in other systems. PBX2 was not expressed or weakly expressed in the primordial follicles. From the primary follicles to the preovulatory follicles, PBX2 expression was inconsistent and the expression was found in the granulosa cell nuclei. The PBX2 expression pattern is similar to HOXA7 expression in ovarian follicular development. Furthermore, FSH down-regulated, GDF-9 did not change PBX2 expression, but co-treatment of the granulosa cells with FSH and GDF-9 up-regulated PBX2 expression. These results implicated a role for PBX2 expression in the steroidogenic activities of granulosa cells in humans. Moreover, PBX2 and HOXA7 bound together to the Pbx sequence, but not to the EMX2 promoter sequence, in SVOG cells. Our findings indicate that HOX cofactors expression in normal human ovary is temporally and spatially specific and regulated by FSH and GDF-9 in granulosa cells. HOX proteins may use different HOX cofactors, depending on DNA sequences that are specific to the granulosa cells.

Breast metastasis from EGFR-mutated lung adenocarcinoma: A case report and review of the literature.

Although lung cancer rarely metastasizes to the breast, we report a case of breast metastasis from lung adenocarcinoma harboring an epidermal growth factor receptor mutation. This breast metastasis was initially considered recurrent breast cancer and was later diagnosed based on histopathological and molecular examinations as metastasis from lung cancer.

Myasthenia gravis induced by nivolumab in patients with non-small-cell lung cancer: a case report and literature review.

A 76-year-old woman who was diagnosed with non-small-cell lung cancer presented with left eyelid ptosis and grade 4 creatine phosphokinase elevation after the second cycle of nivolumab monotherapy. Nivolumab has demonstrated promising efficacy in patients with non-small-cell lung cancer in several trials. Dyspnea and muscle weakness developed rapidly with an acute exacerbation. She underwent plasmapheresis and intravenous immune globulin followed by treatment with low-dose prednisolone. She had gradual symptoms improvement. We diagnosed her with myasthenia gravis (MG) based on her symptoms and the detection of anti-acetylcholine receptor antibody. According to postmarketing surveillance in 15,740 Japanese patients, the total incidence rate of MG is 0.1%. We report a rare case of drug-induced MG in a patient receiving nivolumab.