Comparison of cisplatin-based versus standard preoperative chemotherapy in patients with operable triple-negative breast cancer: propensity score matching and inverse probability of treatment weighting analysis.

PURPOSE: The efficacy of carboplatin is non-equivalent to that of cisplatin (CDDP) for various tumor types in curative settings. However, the role of CDDP in operable triple-negative breast cancer (TNBC) patients remains unknown. We conducted a multicenter observational study to examine the effects of CDDP added to preoperative chemotherapy in patients with TNBC. METHODS: This retrospective study consecutively included previously untreated patients with stage I-III TNBC treated with preoperative chemotherapy with or without CDDP. The primary endpoint was distant disease-free survival (DDFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize confounding biases in comparisons between the two groups. RESULTS: A total of 138 patients were enrolled in the study. Of these, 52 were in the CDDP group and 86 in the non-CDDP group. DDFS was significantly better in the CDDP group than in the non-CDDP group (unadjusted hazard ratio (HR) 0.127 and p < 0.001, PSM HR 0.141 and p < 0.003, IPTW HR 0.123 and p = < 0.001). Furthermore, among the patients with residual cancer burden (RCB) class II/III, DDFS was better in the CDDP group than in the non-CDDP group (unadjusted HR 0.192 and p = 0.013, PSM HR 0.237 and p = 0.051, IPTW HR 0.124 and p = 0.059). CONCLUSION: Our study showed that CDDP-containing regimens achieved favorable prognoses in patients with operable TNBC, especially for the RCB class II/III population. Confirmative studies are warranted to elucidate the role of CDDP in TNBC treatment.

Hepatectomy Followed by Adjuvant Chemotherapy with 3-Month Capecitabine Plus Oxaliplatin for Colorectal Cancer Liver Metastases.

LESSONS LEARNED: Three-month adjuvant capecitabine plus oxaliplatin in combination (CAPOX) appeared to reduce recurrence, with mild toxicity in postcurative resection of colorectal cancer liver metastases (CLM). Recurrence in patients who underwent the 3-month adjuvant CAPOX after resection of CLM was most commonly at extrahepatic sites. BACKGROUND: The role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable colorectal cancer liver metastases (CLM) is still unclear. We evaluated the feasibility of 3-month adjuvant treatment with capecitabine plus oxaliplatin in combination (CAPOX) for postcurative resection of CLM. METHODS: Patients received one cycle of capecitabine followed by four cycles of CAPOX as adjuvant chemotherapy after curative resection of CLM. Oral capecitabine was given as 1,000 mg/m2 twice daily for 2 weeks in a 3-week cycle, and CAPOX consisted of oral capecitabine plus oxaliplatin 130 mg/m2 on day 1 in a 3-week cycle. Primary endpoint was the completion rate of adjuvant chemotherapy. Secondary endpoints included recurrence-free survival (RFS), overall survival (OS), dose intensity, and safety. RESULTS: Twenty-eight patients were enrolled. Median age was 69.5 years, 54% of patients had synchronous metastases, and 29% were bilobar. Mean number of lesions resected was two, and mean size of the largest lesion was 31 mm. Among patients, 20 (71.4%; 95% confidence interval, 53.6%-89.3%) completed the protocol treatment and met its primary endpoint. The most common grade 3 or higher toxicity was neutropenia (29%). Five-year recurrence-free survival and overall survival were 65.2% and 87.2%, respectively. CONCLUSION: Three-month adjuvant treatment with CAPOX is tolerable and might be a promising strategy for postcurative resection of CLM.

Downregulated ATP6V1B1 expression acidifies the intracellular environment of cancer cells leading to resistance to antibody-dependent cellular cytotoxicity.

Among several mechanisms for the resistance of human epidermal growth factor receptor 2-overexpressing (HER2 +) cancer cells to trastuzumab, little is known regarding the mechanism underlying the resistance to trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Cell death due to ADCC is caused by apoptosis of target cells induced by granzymes released from natural killer cells. Because optimal granzyme physiological activity occurs at neutral pH, we assumed that the pH of the intracellular environment influences the cytotoxic effects of granzymes. We established ADCC-resistant cells and compared them with wild-type cells in terms of the expression of intracellular pH-regulating genes. The expression of ATP6V1B1, which encodes a component of vacuolar ATPases, was downregulated in the ADCC-resistant cells. Thus, to functionally characterize ATP6V1B1, we used a CRISPR/Cas9 system to generate ATP6V1B1-knockout SKBR3 and JIMT-1 cells (both HER2 + human breast cancer cell line). The resulting cells exhibited significantly less ADCC than the control SKBR3 and JIMT-1 cells. The intracellular pH of the ATP6V1B1-knockout SKBR3 and JIMT-1 cells was significantly lower than control SKBR3 and JIMT-1cells. An analysis of granzyme dynamics during the ADCC reaction in cancer cells revealed that granzymes degraded intracellularly in the control SKBR3 and JIMT-1 cells and accumulated in ATP6V1B1-knockout cells, but were not cytotoxic. These findings suggest that decreased vacuolar ATPase activity alters the cytoplasmic pH of cancer cells to create an environment that is less suitable for granzyme bioactivity, which adversely affects the induction of apoptosis of cancer cells by NK cells.

Effects of the Ophthalmic Additive Mannitol on Antimicrobial Activity and Corneal Toxicity of Various Preservatives.

Ophthalmic preservatives are indispensable in eye drop formulations, but may be toxic to corneal structures. Corneal damage necessitates the discontinuation of treatment with ophthalmic solutions. Therefore, the development of a new and safe preservative system without corneal toxicity is needed. The present study investigated the effects of mannitol on the antimicrobial activities and corneal toxicities of various preservatives using Escherichia coli and a human corneal epithelial cell line (HCE-T cells). The following preservatives were examined: boric acid (BA), benzalkonium chloride (BAC), methyl parahydroxybenzoate (MP), propyl parahydroxybenzoate (PP), sodium chlorite (SC), and zinc chloride (ZC). The antimicrobial activities and HCE-T-cell toxicities of 50 µg/mL BA, MP, PP, SC, and ZC were reduced by a co-treatment with mannitol (0-300 µg/mL). The suppressed antimicrobial activities of BA, MP, PP, and SC by the co-treatment with mannitol were restored by the application of a mannitol content higher than 500 µg/mL. In contrast to these 5 preservatives, the addition of mannitol did not affect the antimicrobial activity of BAC and attenuated its HCE-T cell toxicity. Therefore, the balance between the contents of mannitol and preservatives is important in co-treatments. The present results will serve as a guide for the future development of eye drop formulations without corneal toxicity.

[A Case of Breast Cancer Treated with Adjuvant Chemotherapy in a Patient Receiving Tacrolimus Medication after Liver Transplantation].

Tacrolimus is a calcineurin inhibitor that has been used to prevent allograft rejection after organ transplantation. We report the case of a living-donor liver transplant recipient with breast cancer who received adjuvant chemotherapy at an appropriate relative dose intensity in spite of a decrease in the trough blood concentration of tacrolimus. The patient was a woman in her 50s who had undergone living-donor liver transplantation because of primary biliary cirrhosis and received maintenance therapy consisting of tacrolimus. She was diagnosed as having locally advanced breast cancer(ER and HER2 positive). After surgery, we administered 4 courses of EC followed by weekly administration of paclitaxel plus trastuzumab. During chemotherapy, although the trough blood concentration of tacrolimus was slightly decreased, neither severe adverse event nor allograft rejection was observed. Recently, organ transplantation outcomes have significantly improved as a result of the progress of immunosuppressive agents. However, the development of malignancies after transplantation is a serious problem.

Evaluation of Dissolution Profile between Original and Generic Products of Zolpidem Tartrate by Microdialysis-HPLC.

The evaluation of the dissolution profile of hypnotic drugs is important to promote switching from original products to generic products by removing distrust in generic hypnotics. In this study, we investigated differences in the dissolution profiles between original and generic products (GE-D, GE-S, and GE-T) in commercially available zolpidem tartrate (ZOL) products using the HPLC method using a connected microdialysis probe (microdialysis-HPLC method). Although the degree of hardness and the disintegration time were not different among the original, GE-S, and GE-T, GE-D was 1.4 times harder than the other products. The disintegration time of GE-D was approximately twice as long as that of the original product. Generic products dissolved rapidly as compared with the original product, however, the dissolution rate in the ZOL powder (milled ZOL product) was not different between the original and generic products. Macrogol 6000 (polyethylene glycol (PEG)-6000) was used in the generic products, and this additive was the only PEG difference from the original product. We investigated whether the PEG in the product affected the solubility of ZOL and found that the addition of PEG-4000 or PEG-6000 significantly increased the dissolution rate. These results suggest that the solubility of ZOL may be increased by PEG when the product is disintegrated, resulting in the increased dissolution rate in the generic products. In conclusion, we found that the difference of PEG affected the dissolution profile in the disintegration process using the microdialysis-HPLC method. This finding can help ensure the safety of milled products and the selection of additives.

Phase I study of primary treatment with 5-FU, oxaliplatin, irinotecan, levofolinate, and panitumumab combination chemotherapy in patients with advanced/recurrent colorectal cancer involving the wild-type RAS gene: the JACCRO CC-14 study.

BACKGROUND: FOLFOXIRI is now regarded as the chemotherapy regimen that offers the best platform for the treatment of colorectal cancer. However, the safety and efficacy of FOLFOXIRI + panitumumab has not been demonstrated. We conducted a phase I study to determine the recommended dose of FOLFOXIRI + panitumumab as first-line treatment for RAS wild-type metastatic colorectal cancer (mCRC). METHODS: Patients received combination therapy consisting of panitumumab (6 mg/kg on day 1) + FOLFOXIRI [irinotecan (CPT-11), oxaliplatin (L-OHP) 85 mg/m2, and folinate (LV) 200 mg/m2] on day 1, followed by fluorouracil (5-FU) 3200 mg/m2 infused as a 46-h continuous infusion starting on day 1) repeated every 2 weeks as first-line treatment of RAS wild-type mCRC patients. A decrease in CPT-11 dose was planned (started at level 1: CPT-11 165 mg/m2). RESULTS: Seven patients were enrolled, and six were assessed for safety and efficacy. Maximum tolerated dose was not reached at level 1; all patients were treated at these levels. The common Grade 3 or 4 relevant toxicities were diarrhea (50%), hypokalemia (33%) and stomatitis (33%). No treatment-related deaths occurred. Of the six patients assessed four had partial response and the two others had stable disease; hence, the response rate was 66.7% (95% confidence interval 28.9-100%) and the disease control rate was 100%. Time to protocol treatment failure was 7.2 (1.4-7.3) months. CONCLUSION: The FOLFOXIRI + panitumumab chemotherapy regimen was well tolerated by our patients with mCRC and showed promising anti-tumor activity. The recommended phase II dose was determined to be the same as the standard doses of this regimen used worldwide.

Development of a broad range of two-colour ozone indicator.

The antiviral and antibacterial properties of ozone gas have been utilised for air and on-site disinfection. However, excess ozone gas exposure is toxic to humans, necessitating the monitoring of exposure levels. While this has been achieved using ozone indicators, determining exposure levels at intermediate time points during exposure remains challenging owing to the current ones being capable of measuring exposure only at endpoints. Shifts in the endpoint are also difficult as the coverage ranges of the indicators are dependent on a single colour dye. The indicator that covers a wide range is desirable to treat various pathogenic microorganisms. The aim of this study was to develop a two-colour ozone indicator with a broad coverage range that does not compromise the performance of the individual dyes. Exposure levels were indicated by visible changes in colour density and phase, aiding the measurement of exposure at the endpoints and during the exposure period, thereby maintaining better safety profiles for exposed individuals. Additionally, a theoretical approach for the development of two-colour indicators has been described.

Applicability of on-site disinfection of personal protective equipment by ozone gas.

On-site disinfection techniques are beneficial during a pandemic when there is a marked shortage of personal protective equipment (PPE), as experienced during the coronavirus disease 2019 outbreak. Ozone gas has been considered an alternative on-site disinfectant during a pandemic because it has antimicrobial activities, can be produced from air by electricity without the need for storage, and can be easily deactivated after use. However, ozone gas might become distributed at the lower layer because it has a larger molecular weight than air. This study aimed to reveal the applicability of ozone gas for the on-site disinfection of PPE. The lockers meant for changing dresses were used as ozone gas exposure boxes, and the distribution of ozone was assayed. Considering that the determined ozone levels were not consistent in the types of ozone analysers, we studied the chemical and biological activities of ozone, which were evenly detected in the locker. The gown in the locker was also uniformly exposed to ozone. Results showed that ozone gas could be used for the on-site disinfection of PPE in a closed box, such as a locker. This finding is valuable during a pandemic when PPE is in short supply.

FOLFIRINOX as First-line Chemotherapy in Japanese Patients Suffering from Metastatic Pancreatic Cancer (KOBE FOLFIRINOX Study).

Background/Aim: FOLFIRINOX (oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin) combination chemotherapy is the gold-standard therapy for advanced pancreatic cancer. In this study, FOLFIRINOX dosages for Japanese patients were established enabling FOLFIRINOX therapy optimization for efficient use. Patients and Methods: Patients with advanced pancreatic cancer were treated with varying doses of FOLFIRINOX to determine the optimum dosage for highest remission outcomes with the least post-chemotherapy toxicities. Results: Patients given 180 mg of irinotecan and a 400 mg bolus of 5-fluorouracil (5-FU) showed a marked difference in outcome when compared to irinotecan 180 mg given without the 5-FU bolus, with the overall response rate being 28%, a survival time of 6.4 months and progression-free survival time of 4.5 months. Conclusion: The optimum dose of FOLFIRINOX was a dosage combination of oxaliplatin 85 mg/m 2 , irinotecan 180 mg/m 2 , l-leucovorin 400 mg/m 2  and 5-FU 2,400 mg/m 2 , administered as a continuous 46-h infusion.

Phase Ib/II study of nivolumab combined with palliative radiation therapy for bone metastasis in patients with HER2-negative metastatic breast cancer.

Radiation therapy (RT) can enhance the abscopal effect of immune checkpoint blockade. This phase I/II study investigated the efficacy and safety of nivolumab plus RT in HER2-negative metastatic breast cancer requiring palliative RT for bone metastases. Cohort A included luminal-like disease, and cohort B included both luminal-like and triple-negative disease refractory to standard systemic therapy. Patients received 8 Gy single fraction RT for bone metastasis on day 0. Nivolumab was administered on day 1 for each 14-day cycle. In cohort A, endocrine therapy was administered. The primary endpoint was the objective response rate (ORR) of the unirradiated lesions. Cohorts A and B consisted of 18 and 10 patients, respectively. The ORR was 11% (90% CI 4-29%) in cohort A and 0% in cohort B. Disease control rates were 39% (90% CI 23-58%) and 0%. Median progression-free survival was 4.1 months (95% CI 2.1-6.1 months) and 2.0 months (95% CI 1.2-3.7 months). One patient in cohort B experienced a grade 3 adverse event. Palliative RT combined with nivolumab was safe and showed modest anti-tumor activity in cohort A. Further investigations to enhance the anti-tumor effect of endocrine therapy combined with RT plus immune checkpoint blockade are warranted.Trial registration number and date of registration UMIN: UMIN000026046, February 8, 2017; ClinicalTrials.gov: NCT03430479, February 13, 2018; Date of the first registration: June 22, 2017.

Effectiveness of eribulin as first-line or second-line chemotherapy for HER2-negative hormone-resistant advanced or metastatic breast cancer: findings from the multi-institutional, prospective, observational KBCRN A001: E-SPEC study.

BACKGROUND: The optimal positioning of eribulin treatment remains unclear. This study aimed to investigate the effectiveness of eribulin administration as first- and second-line chemotherapy in patients with endocrine-resistant advanced or metastatic breast cancer (AMBC) in the real-world clinical setting. METHODS: This multi-institutional prospective cohort study enrolled patients with triple-negative AMBC or estrogen receptor-positive AMBC refractory to at least one previous endocrine therapy. The overall survival (OS) from the start of first-line (OS1) and second-line chemotherapy (OS2) was assessed. Data analysis included real-world chemotherapy sequences of first- to third-line chemotherapy regimens. The adjusted hazard ratio (HR) with 95% confidence interval (CI) for treatment regimen comparison was calculated using a stratified proportional hazards model. RESULTS: Among 201 patients enrolled, 180 were included in the final analysis. Eribulin was administered as first- and second-line chemotherapy to 46 (26.6%) and 70 (47.9%) patients, respectively. Median OS1 and OS2 were 2.25 (95% CI 1.07-2.68) and 1.75 (95% CI, 1.28-2.45) years for first- and second-line eribulin, respectively. Oral 5-FU followed by eribulin had a numerically longer OS1 (2.84 years) than the other sequences. Among patients who proceeded to second-line or later chemotherapy, the median OS1 for those treated with anthracycline or taxane as first- or second-line (n = 98) was 2.56 years (95% CI 2.27-2.74), while it was 2.87 years (95% CI 2.20-4.32) for those who avoided anthracycline and taxane as first- and second-line (n = 48) (adjusted HR, 1.20; 95% CI 0.70-2.06). In the exploratory analysis, OS1 was 2.55 (95% CI 2.14-2.75) and 2.91 years (95% CI 2.61-4.32) for those aged < 65 and ≥ 65 years, respectively (adjusted HR of ≥ 65, 0.91; 95% CI 0.56-1.46). CONCLUSIONS: Eribulin or oral 5-FU administration in first- and second-line chemotherapy without anthracycline/taxane was acceptable in the real-world setting. TRIAL REGISTRATION: This study is registered with Clinical Trials.gov (NCT 02,551,263).

[A case of chronic myeloid leukemia occurring during treatment for chronic lymphocytic leukemia].

Since the progression of chronic lymphocytic leukemia(CLL)is long and requires lengthy primary disease management, the risk of double primary cancers and secondary cancer due to treatment has become an issue in western countries with a high incidence of CLL. However, the coexistence with chronic myeloid leukemia(CML)is rare even in the West, and no cases have been reported in Japan. At this time, we would like to report a rare case of CML coexisting during the progression of CLL. The patient was a 68-year-old woman. As she had entered the advanced stage of B-cell chronic lymphocytic leukemia(B-CLL), fludarabine, a purine analog agent, was administered. Two years later, a high-granulocyte dominant white blood cell count began to appear. BCR/ABL analysis by FISH was 97. 6%positive, and the chromosomal test was t(9:22)(q34:q11), so CML was diagnosed. Coexistence of CML in CLL can mainly be classified into three types; CML preceding CLL, CLL preceding CML, and simultaneous occurrence, and the most common, as in this case, long progression CLL preceding CML. At this time, we performed a mainly bibliographical consideration according to the main occurrence type, including the possibility of secondary CML due to fludarabine.

[Definitive diagnosis of intravascular large B-cell lymphoma by random skin biopsy].

A 69-year-old male was admitted to our hospital for high-grade-fever and body weight loss lasting for a few months. In a previous hospital, extensive laboratory examinations and imaging modalities had failed to establish the origin of the fever. On admission he showed mild anemia, and elevated LDH and CRP, together with a high sIL-2R level, suggesting a possibility of lymphoid malignancy without nodal or solid organ involvements, in particular, intravascular large B-cell lymphoma(IVLBCL). A bone marrow biopsy revealed no abnormal findings except minimal hemophagocytosis. A random skin biopsy was then performed, though no detectable skin lesion was seen. The histological results of the skin materials clearly showed a prominent intravascular large lymphoid cell proliferation with a phenotype of CD20+, CD79a+, CD3- and CD5- in the small vessels. On the basis of these findings, a diagnosis of IVLBCL was established and the patient was treated with(R-)CHOP regimen immediately, which resulted in complete remission following two courses of chemotherapy. Difficulties often arise in the diagnosis of IVLBCL when suspicious lesions suitable for biopsy are lacking. Random skin biopsy would therefore be a useful tool if less invasive measures fail.

Pronociceptive Roles of Schwann Cell-Derived Galectin-3 in Taxane-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting side effect of taxanes such as paclitaxel and docetaxel. Despite the high medical needs, insufficient understanding of the complex mechanism underlying CIPN pathogenesis precludes any endorsed causal therapy to prevent or relieve CIPN. In this study, we report that elevation of plasma galectin-3 level is a pathologic change common to both patients with taxane-treated breast cancer with CIPN and a mouse model of taxane-related CIPN. Following multiple intraperitoneal injections of paclitaxel in mice, galectin-3 levels were elevated in Schwann cells within the sciatic nerve but not in other peripheral organs or cells expressing galectin-3. Consistent with this, paclitaxel treatment of primary cultures of rat Schwann cells induced upregulation and secretion of galectin-3. In vitro migration assays revealed that recombinant galectin-3 induced a chemotactic response of the murine macrophage cell line RAW 264.7. In addition, perineural administration of galectin-3 to the sciatic nerve of naive mice mimicked paclitaxel-induced macrophage infiltration and mechanical hypersensitivity. By contrast, chemical depletion of macrophages by clodronate liposomes suppressed paclitaxel-induced mechanical hypersensitivity despite the higher level of plasma galectin-3. Deficiency (Galectin-3 -/- mice) or pharmacologic inhibition of galectin-3 inhibited paclitaxel-induced macrophage infiltration and mechanical hypersensitivity. In conclusion, we propose that Schwann cell-derived galectin-3 plays a pronociceptive role via macrophage infiltration in the pathogenesis of taxane-induced peripheral neuropathy. Therapies targeting this phenomenon, which is common to patients with CIPN and mouse models, represent a novel approach to suppress taxane-related CIPN. SIGNIFICANCE: These findings demonstrate that the elevation of plasma galectin-3 is a CIPN-related pathologic change common to humans and mice, and that targeting galectin-3 is a therapeutic option to delay CIPN progression.

Clinical Predictive Factors for the Efficacy of Everolimus in Patients With Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer: A Multicenter Retrospective Cohort Study in Japan.

PURPOSE: To investigate the clinical predictive factors for the efficacy of everolimus (EVE) for advanced/metastatic breast cancer (AMBC). METHODS: Routine practice data of consecutive patients with AMBC who received EVE at 5 institutions in western Japan were retrospectively analyzed in this cohort study (study registration no.: UMIN 000032569). The correlation among time to treatment failure (TTF), overall survival (OS), and clinical background was investigated via univariate and multivariate analyses using Cox hazards model for the clinically important variables. RESULTS: A total of 134 patients were included in the analysis. The median TTF and OS were 5.2 months (95% confidence interval [CI]: 4.1-6.4) and 27.3 months (95% CI: 23.7-30.9), respectively. Multivariate analysis showed that dose reduction of EVE from any initial dose was associated with a longer TTF (hazard ratio [HR]: 0.52; 95% CI: 0.32-0.84, P = .007). Meanwhile, very low hormone sensitivity (ie, relapse within the first 2 years during adjuvant endocrine therapy or progression within 3 months of endocrine therapy immediately before EVE) was associated with a shorter TTF (HR: 2.48; 95% CI: 1.49-4.10, P < .001). In the analysis of stratified treatment outcomes, TTF was longer in the group with <3 liver metastases and in groups other than the very low hormone sensitivity group, regardless of the treatment line of EVE. CONCLUSIONS: Low hormone sensitivity and ⩾3 liver metastases were important prognostic factors for the efficacy of EVE. EVE may be less effective in patients with AMBC with these factors, and as such, chemotherapy should be administered instead.

Gene expression profile of peripheral blood mononuclear cells may contribute to the identification and immunological classification of breast cancer patients.

BACKGROUND: It has been reported that the gene expression profile of peripheral blood mononuclear cells (PBMCs) exhibits a unique gene expression signature in several types of cancer. In this study, we aimed to explore the breast cancer patient-specific gene expression profile of PBMCs and discuss immunological insight on host antitumor immune responses. METHODS: We comprehensively analyzed the gene expression of PBMCs by RNA sequencing in the breast cancer patients as compared to that of healthy volunteers (HVs). Pathway enrichment analysis was performed on MetaCoretm to search the molecular pathways associated with the gene expression profile of PBMCs in cancer patients compared with HVs. RESULTS: We found a significant unique gene expression signature, such as the Toll-like receptor (TLR) 3- and TLR4-induced Toll/interleukin-1 receptor domain-containing adapter molecule 1 (TICAM1)-specific signaling pathway in the breast cancer patients as compared to that of healthy volunteers. Distinctive immunological gene expression profiles also showed the possibility of classifying breast cancer patients into subgroups such as T-cell inhibitory and monocyte-activating groups independent of known phenotypes of breast cancer. CONCLUSIONS: These preliminary findings suggest that evaluation of gene expression patterns of PBMCs might be both a less invasive diagnostic procedure and a useful way to reveal immunological insight of breast cancer, including biomarkers for cancer immunotherapy, such as immune checkpoint inhibitor therapy.

Prevalence and risk factors of hepatitis B virus reactivation in patients with solid tumors with resolved HBV infection.

BACKGROUND: Reports of hepatitis B virus (HBV) reactivation in solid tumors are very limited, and their frequencies and risk factors were previously unknown. AIM: To evaluate the prevalence and risk factors of HBV reactivation in patients with solid tumors with resolved HBV infection. METHODS: All 1088 patients with solid tumors were assessed for eligibility; 251 patients had resolved HBV infection (negative for HBs antigen and positive for anti-HBc antibody and/or positive for anti-HBs antibody), and HBV-DNA was assessed for 243 of these patients in whom we analyzed the prevalence of HBV reactivation. Risk factors for HBV reactivation were exploratorily evaluated by analysis of a case-control study. RESULTS: The prevalence of HBV-DNA reactivation was 2.1% (95% confidence interval [CI], 0.3-3.9%). We did not observe any exacerbation of HBV-DNA by early intervention. A low anti-HBs antibody titer (<10.0 mIU/mL) and high average daily dexamethasone dose (>1.0 mg/day) were high risk factors, with odds ratios of 5.94 (95% CI, 1.15-30.6, P = 0.03) and 8.69 (95% CI, 1.27-58.8, P = 0.02), respectively. CONCLUSION: HBV reactivation in solid tumor patients was relatively rare. Therefore, risk factors that can identify targets for HBV screening must be determined in future studies.

Abemaciclib for the treatment of breast cancer.

INTRODUCTION: There have been numerous clinical trials of CDK4/6 inhibitors performed on various carcinomas including breast cancer. One such inhibitor tested and which has ongoing clinical trials for breast cancer is abemaciclib. Abemaciclib is a molecular-targeted agent that targets basic cell cycle regulatory mechanisms. Areas covered: This review discusses the available clinical data and ongoing clinical trials of abemaciclib in breast cancer. Expert opinion: Abemaciclib has demonstrated a clear anti-tumour effect and manageable toxicity against HR-positive, HER2-negative breast cancer in many clinical trials and is expected to be an important standard therapy. However, currently, besides oestrogen receptor expression, there is a definite lack of predictive biomarkers for response and/or tolerance to abemaciclib, which is important for patient selection. Another problem is that its contribution to overall survival (OS) has not been shown. And while two large the phase 3 study highlighted the anti-tumour effect of abemaciclib, the OS results are awaited. Furthermore, the effect on brain metastases is expected to be unique to abemaciclib as the response of brain metastasis in HR-positive breast cancer patients has been confirmed in a few cases with case collection still ongoing.

Improvement of Dissolution Rate and Stability in a Pirenoxine Ophthalmic Suspension by the Bead Mill Methods.

Foreign matter sensation and blurred vision following instillation of ophthalmic suspension are often observed, and remaining of solid particle on cornea is related these side effects. In addition, low dispersion stability in the ophthalmic suspension affects the therapeutic effect. In this study, we have attempted to enhance the dissolution rate and stability of commercially available pirenoxine ophthalmic suspension (CA-pirenoxine eye drops), anti-cataract eye drops, by changes in particle size. Methylcellulose, zirconia beads (0.1 mm) and Micro Smash were used to mill the pirenoxine (bead mill method), and the distribution of particle size was changed to approximately 60-900 nm (nanodispersions) from 70 nm-3 µm (CA-pirenoxine eye drops). The dissolution rate of pirenoxine increased by the bead mill, and the dissolution rate constant in pirenoxine nanodispersions was 2.1-fold than that in CA-pirenoxine eye drops. Moreover, the dispersion stability in nanodispersions also significant higher in comparison with the CA-pirenoxine eye drops. The dispersion ratio in CA-pirenoxine eye drops and pirenoxine nanodispersions at 2 d after suspension was 48%, 99%, respectively. In conclusion, we showed that the dissolution rate and dispersion stability of CA-pirenoxine eye drops were enhanced by the bead mill method. These findings provide significant information that can be used in the design of ophthalmic suspension.