Successful Retreatment of Metastatic Triple-negative Breast Cancer With Immune Checkpoint Inhibitors and Chemotherapy.

BACKGROUND/AIM: The efficacy of retreatment with immune checkpoint inhibitors (ICIs) in programmed death-ligand 1 (PD-L1) positive metastatic or recurrent triple-negative breast cancer (mTNBC) remains unknown. We report a case of a patient with recurrent triple-negative breast cancer who was successfully treated with two different ICIs in combination with chemotherapy. CASE REPORT: A 60-year-old female patient was treated with neoadjuvant chemotherapy consisting of epirubicin + cyclophosphamide (EC) followed by docetaxel (DTX). The tumor shrank with EC, but progressed with DTX. One year after the surgery, the patient presented with multiple lung metastases. The patient received combination therapy with atezolizumab and nab-paclitaxel and achieved a partial response (PR). However, the disease progressed after 6 months. She received eribulin as second-line chemotherapy for 4.5 months, and her treatment was changed to pembrolizumab, carboplatin, and gemcitabine as third-line chemotherapy. The tumor immediately reduced and disappeared after three cycles of this treatment and achieved PR. CONCLUSION: This case illustrated that retreatment with ICIs was effective.

[Chemotherapy-Resistant Breast Cancer and Carcinomatous Pleuritis Successfully Treated with Abemaciclib plus Letrozole Therapy].

A 78-year-old woman was examined in the outpatient department with a chief complaint of swelling of the left breast. Examination confirmed a 10 cm mass in the left breast as along with edema and redness of the skin, following which a diagnosis of invasive micropapillary carcinoma was made after biopsy. The CT imaging showed left chest wall invasion, multiple axillary lymph node metastases, and left carcinomatous pleuritis. Since this a case of advanced breast cancer, we initiated treatment with bevacizumab plus paclitaxel. After 8 months, her medication was changed to eribulin, owing to progression of the cancer, which continued even up to 4 months. We then initiated abemaciclib plus letrozole therapy as the third treatment. We observed tumor reduction and clearing of pleural effusion with no serious adverse events, and continued her therapy for 11 months before the cancer progressed. We report a case of chemotherapy-resistant breast cancer and carcinomatous pleuritis in an older adult patient for which abemaciclib plus letrozole therapy was effective.

Hemodynamic Variability During Drainage of Large Volumes of Malignant Ascites in Patients With Cancer.

This study compared the variability in mean arterial pressure (MAP) during drainage of ascites in patients with cancer who underwent drainage of a large (5-10 L) or small (<5 L) volume of ascites. We prospectively enrolled 50 patients scheduled for cell-free and concentrated ascites reinfusion therapy. Equivalence was considered to be established if the 95% confidence interval (95% CI) for the highest variability rate of MAP was within ±20%. The median volume of ascites removed was 3.30 L (95% CI [2.84, 4.40]) in the small-drainage-volume group (n = 15) and 6.75 L (95% CI [6.40, 7.30]) in the large-drainage-volume group (n = 34). The 95% CIs for the highest variability rates in MAP ranged from -19.60 to -6.23 and from -19.16 to -12.95 (p = .594), respectively, indicating equivalence. These findings indicate that variability in MAP during drainage of ascites is not dependent on drainage volume.

[A Case of Lung Metastasis of the Breast Cancer with a Remarkable Response to Stereotactic Body Radiation Therapy(SBRT)].

A 69-year-old woman admitted to our hospital with the lump in the left breast. Further examination was performed for the lesion, and it was diagnosed as invasive ductal carcinoma. Partial resection and sentinel lymph node biopsy were performed. Pathological diagnosis was metaplastic carcinoma with squamous metaplasia. As the adjuvant treatment, docetaxel and cyclophosphamide(TC)therapy and radiotherapy was performed. Following the treatment of those, tegafur-uracil was administered for 2 years. Three years after the surgery, an isolated lung metastasis was revealed by CT. Capecitabine and cyclophosphamide(XC)therapy was administered, but not effective. Stereotactic body radiation therapy(SBRT)was performed for the lesion. As a result, the metastatic lesion was obscured. Drug therapy was stopped due to adverse events, and she is observed by no medication. Thirty-six months after SBRT and 78 months after the surgery, the patient is alive without recurrence. SBRT could be an effective treatment strategy for the oligometastais of the lung.

Predicting Preoperative Hemodynamic Changes Using the Visual Analog Scale.

PURPOSE: This study aimed to investigate how both visual analog scale cutoff scores and State-Trait Anxiety Inventory scores relate to hemodynamic changes in patients entering the operating theater. DESIGN: A prospective observational study. METHODS: The study subjects included 130 prospectively enrolled patients who were scheduled for abdominal surgery under combined epidural-general anesthesia and who underwent preoperative anxiety level measurements using both scales. FINDINGS: The heart rate and systolic blood pressure on entering the operating theater were significantly higher than those at baseline in the high and low/moderate anxiety groups. Variations in heart rate and systolic blood pressure were significantly higher, whereas peripheral blood flow was significantly lower in the high anxiety group compared with the low/moderate anxiety group. CONCLUSIONS: Using the visual analog scale to measure anxiety can improve our understanding of the hemodynamic changes that occur when patients enter the operating theater.

A randomised controlled trial of the resistive heating blanket versus the convective warming system for preventing hypothermia during major abdominal surgery.

We compared resistive heating (RH) and upper-body convective warming (CW) in 70 patients (RH 33, CW 31, 6 excluded) undergoing major abdominal surgery. The effect of RH was not inferior to that of CW for the time-weighted average core temperature, and the lower limit of 95% CW was greater than -0.5 degrees C. Resistive heating showed no inferiority in maintaining core temperature compared with convective warming.

[Combination of trastuzumab, aromatase inhibitor and anti-cancer drugs obtained a good prognosis for an inoperable stage III B breast cancer patient with giant skin ulceration].

A 68-year-old woman who had an inoperable, ER-positive, PgR-positive and HER2-positive advanced breast cancer with giant skin ulceration has been treated with the combination of trastuzumab, aromatase inhibitor and anti-cancer drugs. She was thus well-controll for over 9 years. Trastuzumab was administered more than 400 times, but no cardiac toxicity has been observed. The synergistic efficacy of the combination of trastuzumab and anti-cancer drugs was already proven, but it has recently been reported that concurrent treatment of trastuzumab and endocrine therapy improves the prognoses of triple positive breast cancer patients.

Quantitation of Aurora kinase A gene copy number in urine sediments and bladder cancer detection.

BACKGROUND: Chromosome missegregation and the resulting aneuploidy is a common change in neoplasia. The Aurora kinase A (AURKA) gene, which encodes a key regulator of mitosis, is frequently amplified and/or overexpressed in cancer cells, and the level of AURKA amplification is associated with the level of aneuploidy. We examined whether AURKA gene amplification is a biomarker for the detection of bladder cancer. METHODS: The effect of ectopic expression of Aurora kinase A (AURKA) using an adenoviral vector in simian virus 40-immortalized urothelial cells (SV-HUC) on centrosome multiplication and chromosome copy number was measured in vitro by immunofluorescence and fluorescence in situ hybridization (FISH), respectively. The FISH test was also used to examine AURKA gene copy number in exfoliated cells in voided urine samples from 23 patients with bladder cancer and 7 healthy control subjects (training set), generating a model for bladder cancer detection that was subsequently validated in an independent set of voided urine samples from 100 bladder cancer patients and 148 control subjects (92 healthy individuals and 56 patients with benign urologic disorders). An AURKA gene score (the proportion of cells with three or more AURKA signals) was used to produce receiver operating characteristic (ROC) curves and to calculate the specificity and sensitivity of the AURKA FISH test. Differences between mean AURKA scores in different pathogenetic groups of bladder cancer stratified according to histological grade and stage were tested by unpaired Mann-Whitney t tests or one-way Wilcoxon tests. All statistical tests were two-sided. RESULTS: Forced overexpression of AURKA in urothelial cells induced amplification of centrosomes, chromosome missegregation, and aneuploidy, and natural overexpression was detectable in in situ lesions from patients with bladder cancer. The FISH test for the AURKA gene copy number performed on the validation set yielded a specificity of 96.6% (95% confidence interval [CI] = 92.3% to 98.5%) and sensitivity of 87% (95% CI = 79.0% to 92.2%) and an area under the ROC curve of 0.939 (95% CI = 0.906 to 0.971; P < .001). CONCLUSION: Overexpression of AURKA can cause aneuploidy in urothelial cells, and the AURKA gene copy number is a promising biomarker for detection of bladder cancer.

Characterization of a panel of cell lines derived from urothelial neoplasms: genetic alterations, growth in vivo and the relationship of adenoviral mediated gene transfer to coxsackie adenovirus receptor expression.

PURPOSE: Cell lines have become an essential component for the investigation of cancer. We have developed a panel of cell lines derived from human urothelial cancers and we describe some of their important characteristics. MATERIALS AND METHODS: Ten human urothelial cancer cell lines were characterized by their growth in athymic nude mice, CAR expression and their susceptibility to adenoviral mediated transfer of the green fluorescence protein gene. TP53 mutation status and immunochemical analysis of p53, pRB and p16 were also examined. RESULTS: Five cell lines rapidly produced tumors in athymic nude mice. Two cell lines produced tumors in 1 month, 1 produced them in 3 months and 2 were nontumorigenic. The cell lines varied in CAR expression and in their susceptibility to adenoviral mediated gene transduction. There was no direct correlation between CAR expression and susceptibility to adenoviral mediated gene transduction. Seven cell lines had TP53 mutations, of which 2 had large deletions and did not express p53 protein by immunostaining. All cell lines expressed abnormal pRB by immunochemical analysis (3 had no staining and 7 had homogenously strong staining) and 8 did not express p16 (7 showed homogeneously strong pRB staining). CONCLUSIONS: Our panel of 10 human urothelial cell lines differed in genetic alterations, growth in nude mice, susceptibility to adenoviral mediated gene transduction, and expression of p53, p16 and pRB. The availability of various urothelial cancer cell lines with differing genotypic and phenotypic features will facilitate further research into bladder cancer.

Tumor-specific exon creation of the HELLS/SMARCA6 gene in non-small cell lung cancer.

To identify tumor-suppressor genes on chromosome 10 in non-small cell lung cancers, we isolated 10 types of splicing variant of the HELLS/SMARCA6 gene transcripts. HELLS/SMARCA6 is a novel member of SNF2 family, which is implicated in cellular functions like chromatin remodeling. Variant 1 was an alternatively spliced isoform containing an insertion of a 44 ntd intronic sequence between exons 3 and 4, giving rise to a premature termination of translation. Expression of variant 1 was detected exclusively in lung cancer specimens (11 of 43 cases, 26%) but was not detected in corresponding normal tissues. The D10S520 marker in the proximity of the HELLS/SMARCA6 gene showed prevalent allelic loss (41%) compared to flanking markers (25-31%). These results suggest that loss of function of HELLS/SMARCA6 by allelic loss and aberrant proteins by tumor-specific exon creation may result in epigenetic deregulation, leading lung cells to malignancy or its progression.

Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation.

Bcl-2 is associated with resistance to radiotherapy in prostate cancer. It was recently demonstrated that transduction of LNCaP prostate cells with the PTEN gene resulted in Bcl-2 downregulation. We hypothesized that forced expression of PTEN in prostate cancer cells would sensitize cells to radiation, downregulate Bcl-2 expression, and potentiate the G2M block induced by radiation. Four cell lines - PC-3-Bcl-2 (Bcl-2 overexpression, deleted PTEN), PC-3-Neo (wild-type Bcl-2, deleted PTEN), LNCaP (Bcl-2 overexpression, deleted PTEN), and DU-145 (wild-type Bcl-2 and PTEN) - were transduced with a recombinant adenovirus-5 vector expressing the human wild-type PTEN cDNA under the control of a human cytomegalovirus promoter (Ad-MMAC). After correction for the effect of Ad-MMAC on plating efficiency, Ad-MMAC treatment reduced the surviving fractions after 2 Gy as follows: PC-3-Bcl-2, from 60.5 to 3.6%; PC-3-Neo, no reduction; LNCaP, from 29.6 to 16.3%; and DU-145, from 32.7 to 25.7%. PTEN expression was associated with the downregulation of Bcl-2 expression in PC-3-Bcl-2 and LNCaP cell lines. Ad-MMAC plus radiotherapy potentiated the G2M block seen with radiotherapy alone only in PC-3-Bcl-2 cells. These findings suggest that overexpression of Bcl-2 result in radioresistance and inability of radiation to cause its typical G2M cell-cycle arrest.