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1.
Breast Cancer Res Treat ; 204(2): 261-275, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38123790

RESUMO

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.


Assuntos
Cisplatino , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/cirurgia , Estudos Retrospectivos , Pontuação de Propensão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Neoadjuvante
2.
Heliyon ; 9(2): e13360, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36776915

RESUMO

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.

3.
Sci Rep ; 12(1): 22397, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36575361

RESUMO

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.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Nivolumabe/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Progressão , Metástase Neoplásica
4.
Breast Cancer ; 29(5): 796-807, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35460066

RESUMO

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).


Assuntos
Neoplasias da Mama , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Fluoruracila/uso terapêutico , Furanos , Hormônios/uso terapêutico , Humanos , Cetonas , Estudos Prospectivos , Receptor ErbB-2 , Taxoides/efeitos adversos
5.
Cancer Diagn Progn ; 2(1): 101-106, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35400007

RESUMO

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.

6.
Oncologist ; 26(7): e1125-e1132, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33977607

RESUMO

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.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Fluoruracila/efeitos adversos , Hepatectomia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Oxaliplatina/uso terapêutico
7.
Cancer Res ; 81(8): 2207-2219, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33608316

RESUMO

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.


Assuntos
Galectinas/sangue , Macrófagos/fisiologia , Percepção da Dor/fisiologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Células de Schwann/metabolismo , Nervo Isquiático/metabolismo , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Proteínas Sanguíneas/antagonistas & inibidores , Proteínas Sanguíneas/farmacologia , Proteínas Sanguíneas/fisiologia , Movimento Celular , Quimiotaxia , Ácido Clodrônico/farmacologia , Modelos Animais de Doenças , Docetaxel/efeitos adversos , Feminino , Galectinas/antagonistas & inibidores , Galectinas/farmacologia , Galectinas/fisiologia , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/sangue , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Estudos Prospectivos , Ratos , Células de Schwann/efeitos dos fármacos , Nervo Isquiático/citologia , Nervo Isquiático/efeitos dos fármacos , Regulação para Cima
8.
Cancer Immunol Immunother ; 70(3): 817-830, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33000417

RESUMO

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.


Assuntos
Citotoxicidade Celular Dependente de Anticorpos , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Neoplasias/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , ATPases Vacuolares Próton-Translocadoras/genética , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células , Imunofluorescência , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Concentração de Íons de Hidrogênio , Imuno-Histoquímica , Espaço Intracelular/metabolismo , Terapia Neoadjuvante , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Resultado do Tratamento , ATPases Vacuolares Próton-Translocadoras/metabolismo
9.
Chem Pharm Bull (Tokyo) ; 68(11): 1069-1073, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33132373

RESUMO

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.


Assuntos
Anti-Infecciosos/química , Escherichia coli/efeitos dos fármacos , Manitol/farmacologia , Soluções Oftálmicas/química , Conservantes Farmacêuticos/farmacologia , Anti-Infecciosos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Córnea/citologia , Córnea/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Conservantes Farmacêuticos/química
10.
Gan To Kagaku Ryoho ; 47(1): 83-85, 2020 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-32381868

RESUMO

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.


Assuntos
Neoplasias da Mama , Transplante de Fígado , Tacrolimo/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Doadores Vivos , Pessoa de Meia-Idade
11.
Breast Cancer (Auckl) ; 13: 1178223418825135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30733627

RESUMO

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.

12.
Chem Pharm Bull (Tokyo) ; 67(2): 120-124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30713271

RESUMO

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.


Assuntos
Medicamentos Genéricos/análise , Zolpidem/análise , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Medicamentos Genéricos/química , Microdiálise , Polietilenoglicóis , Solubilidade , Zolpidem/química
13.
Asia Pac J Clin Oncol ; 15(1): 63-68, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29984542

RESUMO

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.


Assuntos
Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/epidemiologia , Hepatite B/virologia , Neoplasias/tratamento farmacológico , Ativação Viral/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Estudos de Casos e Controles , Feminino , Hepatite B/tratamento farmacológico , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/virologia , Prevalência , Estudos Retrospectivos , Fatores de Risco
14.
Breast Cancer ; 26(3): 282-289, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30317464

RESUMO

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.


Assuntos
Neoplasias da Mama/imunologia , Leucócitos Mononucleares/metabolismo , Transcriptoma , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Análise por Conglomerados , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Transdução de Sinais
15.
Expert Opin Pharmacother ; 19(5): 517-524, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29522364

RESUMO

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.


Assuntos
Aminopiridinas/uso terapêutico , Benzimidazóis/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Aminopiridinas/farmacocinética , Benzimidazóis/farmacocinética , Biomarcadores/análise , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/metabolismo , Quimioterapia Combinada , Estradiol/análogos & derivados , Estradiol/uso terapêutico , Feminino , Fulvestranto , Humanos , Estadiamento de Neoplasias , Prognóstico
16.
Int J Clin Oncol ; 23(3): 490-496, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29464396

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Irinotecano , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Panitumumabe , Resultado do Tratamento , Proteínas ras/genética
17.
Mol Clin Oncol ; 7(3): 347-350, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28894576

RESUMO

Combination chemotherapy with capecitabine and oxaliplatin for gastric cancer (G-XELOX) is considered as a potentially promising regimen. However, the use of the G-XELOX regimen in Japanese patients has not been investigated to date, and recommended doses of G-XELOX for Japanese patients with metastatic gastric cancer have not been established. The aim of the present study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) for systemic chemotherapy with G-XELOX for metastatic gastric cancer. The enrolled patients received systemic chemotherapy with oxaliplatin 130 mg/m2 on day 1 and capecitabine 2,000 mg/m2/day, b.i.d. for 14 days, repeated every 3 weeks. A decrease in oxaliplatin dose was planned from start level 1 (130 mg/m2). A total of 6 patients were enrolled between January and July 2015. MTD was not reached at level 1. Oxaliplatin 130 mg/m2 in combination with capecitabine 2,000 mg/m2/day b.i.d. could be administered with acceptable toxicity, and all patients were treated at these doses. One case of grade 3 stomatitis was considered as a dose-limiting toxicity at level 1; however, excluding this case, no grade 3 or 4 non-hematological toxicity was observed. There were no treatment-related deaths. The median relative dose intensity was 71.3% for capecitabine and 92.1% for oxaliplatin. Of the 6 patients, 3 had measurable lesions according to the Response Evaluation Criteria In Solid Tumors; the response rate and disease control rate were both 67%. Therefore, systemic chemotherapy with G-XELOX was well-tolerated by patients with advanced gastric cancer. The RD was defined as oxaliplatin 130 mg/m2 in combination with capecitabine 2,000 mg/m2/day b.i.d.

18.
ESMO Open ; 2(1): e000130, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28761726

RESUMO

BACKGROUND: The prognosis of locally advanced gastric cancer, such as clinical T4 disease, bulky nodal involvement, type 4 and large type 3 gastric cancer, remains unsatisfactory, even with D2 gastrectomy followed by adjuvant chemotherapy. One promising approach is neoadjuvant chemotherapy. Combination chemotherapy with S-1 and oxaliplatin (SOX) is recognised as a potentially promising regimen for gastric cancer. However, the use of neoadjuvant chemotherapy consisting of SOX for locally advanced gastric cancer has not been reported. The aim of this study was to determine the maximum tolerated dose (MTD) and recommended dose of preoperative chemotherapy combined with SOX for locally advanced gastric cancer. METHODS: Patients received two cycles of neoadjuvant chemotherapy with oxaliplatin on day 1, as well as S-1 (80 mg/m2/day, twice daily) for 14 days, repeated every 3 weeks. They then underwent gastrectomy with curative D2/3 lymph node dissection followed by adjuvant S-1 (80 mg/m2/day, twice daily) for 1 year. Escalation of oxaliplatin dose was planned (starting at level 0, oxaliplatin 100 mg/m2; level 1, 130 mg/m2). RESULTS: Six patients were enrolled. MTD was not reached at level 1. Oxaliplatin 130 mg/m2 in combination with S-1 80 mg/m2/day twice daily could be administered with acceptable toxicity. Peripheral neuropathy was observed in all patients but with no functional disorders. No treatment-related death was observed and the incidence of operative morbidity was tolerable. Resection with curative intent was undertaken in all patients with R0 resection performed in five (83%) and R1 in one. Two of the six patients had a pathological complete response (33%). CONCLUSION: Neoadjuvant chemotherapy with an SOX regimen was feasible in patients with locally advanced gastric cancer. The recommended phase II dose was determined to be oxaliplatin 130 mg/m2 in combination with S-1 80 mg/m2/day, twice daily.

19.
Anticancer Res ; 37(7): 3703-3710, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28668863

RESUMO

AIM: To determine the recommended dose of neoadjuvant chemotherapy of combined capecitabine and oxalipatin (G-XELOX) for locally advanced gastric cancer. PATIENTS AND METHODS: Patients received two cycles of neoadjuvant chemotherapy with oxaliplatin on day 1 and capecitabine (2,000 mg/m2/day, b.i.d.) on days 1-14, repeated every 3 weeks. They then underwent gastrectomy with curative D2/3 lymph-node dissection followed by adjuvant therapy with S-1 for 1 year. De-escalation of oxaliplatin dose was planned (starting at level 1, oxalipatin 130 mg/m2). RESULTS: Six patients were enrolled. The maximum tolerated dose was not reached at level 1. Oxaliplatin at 130 mg/m2 combined with capecitabine at 2,000 mg/m2/day, b.i.d. had acceptable toxicity. No treatment-related death occurred. Most frequent drug-related adverse events during neoadjuvant G-XELOX were nausea and peripheral sensory neuropathy. One patient declined surgical resection, leaving five undergoing resection with curative intent, of whom four achieved pathological down-staging after neoadjuvant G-XELOX. CONCLUSION: Neoadjuvant G-XELOX was feasible in patients with locally advanced gastric cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Neoplasias Gástricas/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Capecitabina/uso terapêutico , Combinação de Medicamentos , Feminino , Gastrectomia , Humanos , Masculino , Dose Máxima Tolerável , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Ácido Oxônico/efeitos adversos , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/efeitos adversos , Tegafur/uso terapêutico
20.
Yakugaku Zasshi ; 137(5): 635-641, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28458295

RESUMO

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.


Assuntos
Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Oxazinas , Metilcelulose , Nanopartículas , Soluções Oftálmicas , Oxazinas/efeitos adversos , Tamanho da Partícula , Suspensões , Zircônio
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