RESUMO
Case 1: A 48-year-old woman, had right breast cancer with multiple liver metastases. Seven courses of paclitaxel plus bevacizumab were administered, but due to disease progression, 12 courses of FEC 75(total epirubicin 900 mg/m2)were administered. 2 months after the last FEC administration, the patient developed heart failure and died about 3 months later. Case 2: A 58-year-old woman, was on endocrine therapy after surgery for left breast cancer. Recurrence of lung and bone metastases were appeared 5 years after surgery, 10 courses of FEC 75(total epirubicin 750 mg/m2)were administered due to disease progression. Eight months after the last administration of FEC, the patient developed heart failure and died about 8 months later. Anthracycline induced cardiotoxicity is irreversible and has a severe course. Therefore, anthracycline should be administered with caution.
Assuntos
Antraciclinas , Neoplasias da Mama , Insuficiência Cardíaca , Feminino , Humanos , Pessoa de Meia-Idade , Antraciclinas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Progressão da Doença , Epirubicina/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Recidiva Local de Neoplasia , PaclitaxelRESUMO
Case 1: A 73-year-old man underwent total gastrectomy for residual gastric cancer, and final pathological diagnosis was pStage â B. Adjuvant chemotherapy was not performed. CT findings showed multiple liver metastasis 16 months after procedure. S-1 and CDDP were administered for 28 months. Although chemotherapy regimen was changed to S-1, paclitaxel plus ramucirumab, nivolumab, irinotecan and S-1 plus oxaliplatin(SOX)after progression, he died 73 months after operation, and 57 months after recurrence. Case 2: A 72-year-old man was pointed out swelling of gastric lymph nodes in CT imaging. He was diagnosed as advanced gastric cancer with para-aortic lymph node metastasis by followed examination. S- 1 plus CDDP was administrated for 30 months. S-1 and SOX were administered after progressive findings, but he died 48 months after diagnosis. We report 2 cases of recurrent and advanced gastric cancer with long-term survival because of successful chemotherapy.
Assuntos
Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gastrectomia , Humanos , Metástase Linfática , Masculino , Recidiva Local de Neoplasia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgiaRESUMO
A 68-year-old woman was receiving chemotherapy and endocrine therapy for right breast cancer postoperative pulmonary metastasis and local lymph node recurrence. However, she developed interstitial pneumonia 12 weeks after initiating treatment with everolimus and exemestane. Treatment with everolimus and exemestane was discontinued and steroid pulse therapy was initiated; however, she required ventilator management because of the severity of the pneumonia. The patient's condition improved 9 days after ventilator management. Everolimus-induced interstitial pneumonia is often mild, but it can be severe in rare cases. In our case, everolimus-induced diffuse alveoli damage was successfully treated with ventilator management.
Assuntos
Neoplasias da Mama , Doenças Pulmonares Intersticiais , Pneumonia , Idoso , Androstadienos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Everolimo/efeitos adversos , Feminino , Humanos , Recidiva Local de NeoplasiaRESUMO
Case 1: A60-year-old man underwent resection of a brain tumor, which was pathologically diagnosed as adenocarcinoma. As he was diagnosed with unresectable rectal cancer due to pulmonary metastasis, we performed abdominoperineal resection after chemotherapy. Since pulmonary metastasis and local recurrence were detected 1 year after the surgery, he was administered chemotherapy. He died 37 months after the surgery. Case 2: A6 4-year-old man was diagnosed with unresectable rectal cancer due to pulmonary and hepatic metastases, resulting in an examination for melena. We performed laparoscopic low anterior resection and hepatic partial resection after chemotherapy. No relapse has occurred 1 year after the surgery. Case 3: A39 -year-old man was examined for abdominal pain and distension and was diagnosed with unresectable rectal cancer due to invasion of the left ureter and multiple hepatic metastases. We performed anterior resection, hepatic partial resection, and RFAafter chemotherapy. He has remained in relapse-free survival for 15 months after the surgery. These results suggest that curative resection after chemotherapy improves the prognosis of unresectable colorectal cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de NeoplasiaRESUMO
BACKGROUND: Although the S-1 plus CDDP(SP)regimen is the standard treatment for advanced gastric cancer, hydration and admission have been recommended after cisplatin has been administered. In this study, short hydration(SH)method was used and SP was administered in outpatient settings. We evaluated renal toxicity of cisplatin in the SH-SP regimen at our hospital. METHODS: Eleven of 16 patients(5 underwent only 1 course and so were excluded)received the SH-SP regimen between January 2012 and January 2018 to present and were included. Serum creatinine(Cr)and estimated glomerular filtration rate(eGFR)were used to assess renalfunction. RESULTS: Median course was 5. Rate of 5-course accomplishment was 72.7%. Grade 1 Cr elevation was observed in only 3 patients and there was no severe renal disorder. CONCLUSION: The SHSP regimen could be administered in outpatient settings and was considered safe as it did not cause renal toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Nefropatias , Neoplasias Gástricas/tratamento farmacológico , Cisplatino , Combinação de Medicamentos , Humanos , Pacientes Ambulatoriais , Ácido Oxônico , TegafurRESUMO
A 50-year-old woman was referred to our hospital due to breast cancer with multiple liver metastasis diagnosed by CT scan. Laboratory findings showed liver dysfunction(T-Bil 7.6mg/dL)with marked elevation of tumor markers(CEA 727.9 ng/mL). Breast tumor biopsy showed an invasive ductal carcinoma(scirrhous type), ER(+), PgR(-), and HER2(3+). Combination therapy with docetaxel, carboplatin and, trastuzumab was administered after the end of 1 course of weekly paclitaxel plus bevacizumab regimen. The patient maintained a good condition without liver dysfunction 8 months after the first visit. Follow-up CT scan showed partial response of breast and hepatic tumors. Our case suggests that careful chemotherapy can improve the prognosis of breast cancer with liver metastasis even if a patient is in an icteric condition.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama , Carcinoma Ductal de Mama , Icterícia , Neoplasias Hepáticas , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/secundário , Feminino , Humanos , Icterícia/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , PaclitaxelRESUMO
BACKGROUND/AIMS: Lysyl oxidase (LOX) family members play a key role in modifying the primary tumor microenvironment by crosslinking collagens and elastin in the extracellular matrix. The aim of this study was to analyze the LOX-like (LOXL)1, LOXL3, and LOXL4 expressions in gastric cancer tissue by immunohistochemical staining. METHODS: The correlations between the clinicopathological features of 597 primary gastric carcinomas and LOX family members - LOXL1, LOXL3, and LOXL4 - were investigated by immunohistochemical studies. The effect of the transforming growth -factor ß1 (TGFß1) on the expressions of LOXL1, LOXL3, and LOXL4 in gastric cancer was examined using diffuse-type gastric cancer cell lines in vitro. RESULTS: The expressions of LOXL1, LOXL3, and LOXL4 were correlated with T invasion, lymph node metastasis, and lymphatic and venous invasion. LOXL1 expression was associated with histological intestinal-type and expanding growth patterns. The overall survival of patients with LOXL1-, LOXL3-, or LOXL4-positive cancer was poorer than those with negative cancer. LOXL3 and LOXL4 mRNA expressions were significantly high in diffuse-type gastric cancer cells with high invasion ability. TGFß decreased the LOXL1 expression and increased LOXL3 and LOXL4 expression. CONCLUSION: LOXL1, LOXL3, and LOXL4 expressions are associated with distant metastasis of gastric cancer.
Assuntos
Aminoácido Oxirredutases/metabolismo , Carcinoma/patologia , Neoplasias Gástricas/patologia , Carcinoma/genética , Carcinoma/mortalidade , Linhagem Celular Tumoral , Feminino , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Proteína-Lisina 6-Oxidase , Proteínas Recombinantes/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Fator de Crescimento Transformador beta1/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Intracystic papillary carcinoma (IPC) is defined as cancer that develops from the wall of a cyst in the breast. As breast cancer in men accounts for only 1% of all breast cancers, male IPC is an extremely rare form of the disease. The present case report examines IPC in a man, along with an in-depth literature discussion. CASE PRESENTATION: A 64-year-old Japanese man noticed a mass in the right breast and sought medical attention. An elastic and soft neoplastic 3-cm lesion was palpated in the right papilla. As a 1-cm solid tumor with a gradual rise from the cyst wall was confirmed within the cyst, vacuum-assisted biopsy (VAB) was performed on that site. Pathological examination of the biopsy revealed heterotypic cells with an enlarged oval nucleus forming dense papillary structures mainly of vascular connective tissue component. Contrast-enhanced computed tomography (CT) confirmed thickening of the wall that protruded outside the cyst. The preoperative diagnosis was right breast cancer (male IPC) TisN0M0 stage 0 luminal B-like. Total mastectomy and sentinel lymph node biopsy were performed. In the excised specimen, a 4.0-cm unilocular cyst was found, along with a 1-cm solid tumor with a gradual rise from the cyst wall. Pathological diagnosis of the resected specimen shared similar characteristics with the solid tumor in the cyst: notably, an oval nucleus with histologically clear nucleolus and fine granular chromatin, cylindrically shaped heterotypic cells, and the presence of basophilic cells in the papillary growth with a thin stem of fibrovasculature as the axis. Some invasion of tumor cells into the interstitium was confirmed. As such, the final diagnosis was right breast cancer (male IPC) T2N0M0 stage IIA luminal B-like. The expression of hormone receptor (ER and PgR) was high, and endocrine therapy was initiated postoperatively (20 mg/day tamoxifen). At the present time (3 months postoperation), there has not been any evidence of metastasis. CONCLUSIONS: We reported a rare case of an IPC in the male breast, along with a literature review.
Assuntos
Neoplasias da Mama Masculina/patologia , Carcinoma Papilar/patologia , Cistos/patologia , Neoplasias da Mama Masculina/cirurgia , Carcinoma Papilar/cirurgia , Cistos/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Biópsia de Linfonodo SentinelaRESUMO
An 86-year-old woman visited our hospital with a tumor on her right axilla. Ultrasonography(US)showed a 4 cm tumor between mammary gland and axilla with swelling of some lymph nodes. No distant metastatic lesions were found. The pathological findings revealed breast apocrine carcinoma; therefore, we performed total mastectomy and axillary lymph node dissection. The postoperative pathological findings revealed breast apocrine carcinoma with pT4N2M0, Stage â ¢b(ER positive, PgR negative, HER2 positive, Ki-67 6%). We present a case of breast apocrine carcinoma confused with axially apocrine adenocarcinoma during the diagnosis and report the relevant literature.
Assuntos
Adenocarcinoma , Neoplasias da Mama , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos , Metástase Linfática , MastectomiaRESUMO
A 61-year-old woman with a breast tumor detected by mammography examination was admitted to our hospital. Ultrasonography showed a 15.5×7.2mm sized irregular mass at the left BD area. Vacuum-assisted biopsy did not reveal any malignant cells. After 3 months, ultrasonography reexamination showed that the irregular mass had increased to 24.2×16.5mm in size, and it had spread to multiple axillary lymph nodes. The patient was diagnosed with breast cancer by core needle biopsy of the axillary lymph node. Total mastectomy with axillary lymph node dissection was performed. The pathological diagnosis was solid-tubular carcinoma with infarcted necrosis. The number of metastatic axillary lymph nodes was confirmed to be 23 in total. This case was considered very rare and important because there have been very few reports of breast cancer with infarcted necrosis.
Assuntos
Neoplasias da Mama , Linfonodos , Metástase Linfática , Mastectomia , Axila , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Pessoa de Meia-Idade , Necrose/diagnóstico , Necrose/cirurgia , Biópsia de Linfonodo SentinelaRESUMO
In recent years, breast micro-lesions such as ductal carcinoma in situ(DCIS)were detected with progress of the image diagnosis. We investigated the usefulness of vacuum-assisted biopsy(VAB)for initial biopsy of breast tumors. We analyzed 32 cases of VAB performed for breast tumors. The pathological diagnosis of the biopsy specimens was malignant lesions in 10 cases, border-line lesions in 1 and benign lesions in 21 cases. 11 cases underwent surgery and the final histopathological diagnosis was the same in 10 of them. One case histopathology varied from DCIS to invasive ductal carcinoma(IDC). It was suggested that VAB at initial biopsy was a useful biopsy method.
Assuntos
Biópsia por Agulha , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Humanos , VácuoRESUMO
The aim of this study was to analyze the significance of glucose metabolism-related enzymes in the proliferation of gastric cancer under hypoxia. Four hypoxia-resistant gastric cancer cell lines and four parent cell lines were used. Reverse transcription-PCR was used to evaluate the mRNA expression levels of the following metabolism-related enzymes: pyruvate kinase isozyme M2 (PKM2), glutaminase (GLS), enolase 1 (ENO1), glucose-6-phosphate dehydrogenase (G6PDH), and PKM1. The effects of these enzymes on the proliferation of gastric cancer cells were examined using siRNAs, shikonin as a PKM2 inhibitor, or BPTES as a GLS inhibitor, in vitro and in vivo. Levels of both PKM2 and GLS mRNA were significantly high in all hypoxia-resistant cell lines, compared with those of their parent cells. Knockdown of PKM2 and GLS significantly decreased the proliferation of all hypoxia-resistant cells. The combination of siPKM2 and siGLS significantly decreased proliferation compared with treatment by siPKM2 or siGLS alone. The knockdown of ENO1, G6PDH, or PKM1 did not decrease the proliferation of all hypoxia-resistant cells. Combination treatment using shikonin and BPTES inhibited the proliferation of all hypoxia-resistant cancer cells more than that by either agent alone. The in vivo study indicated that the tumor size treated by the combination of shikonin and BPTES was significantly smaller than that of vehicle-treated group. These findings suggested that PKM2 and GLS might play important roles in the proliferation of hypoxic gastric cancer cells. A combination of PKM2 and GLS inhibitors could be therapeutically promising for the treatment of gastric cancer.
Assuntos
Proteínas de Transporte/metabolismo , Glutaminase/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Gástricas/patologia , Hormônios Tireóideos/metabolismo , Animais , Antineoplásicos/farmacologia , Hipóxia Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Gástricas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Ligação a Hormônio da TireoideRESUMO
Tumor stromal cells play a critical role in the progression of diffuse-type gastric cancer (DGC). The aim of this study was to clarify where tumor stromal cells originate from and which factor(s) recruits them into the tumor stroma. Immunodeficient mice with bone marrow transplantation from the cytomegalovirus enhancer/chicken ß-actin promoter-enhanced green fluorescent protein mice were used for the in vivo experiments. An in vitro study analyzed the chemotaxis-stimulating factor from DGC cells using bone marrow-derived mesenchymal cells (BM-MCs). The influences of chemokine (C-X-C motif) receptor 2 (CXCR2) inhibitor on the migration of BM-MCs were examined both in vitro and in vivo. BM-MCs frequently migrated into stroma of DGC in vivo. The number of migrating BM-MCs was increased by conditioned medium from DGC cells. CXCL1 from DGC cells stimulated the chemoattractant ability of BM-MCs. Both anti-CXCL1 antibody and CXCR2 inhibitor decreased the migration of BM-MCs, stimulated by DGC cells. A CXCR2 inhibitor, SB225002, reduced the recruitment of BM-MCs into the tumor microenvironment in vivo, decreasing tumor size and lymph node metastasis, and prolonging the survival of gastric tumor-bearing mice. These findings suggested that most tumor stromal cells in DGC might originate from BM-MCs. CXCL1 from DGC cells stimulates the recruitment of BM-MCs into tumor stroma via CXCR2 signaling of BM-MCs. Inhibition of BM-MC recruitment via the CXCL1-CXCR2 axis appears a promising therapy for DGC.
Assuntos
Quimiocina CXCL1/metabolismo , Células-Tronco Mesenquimais/metabolismo , Receptores de Interleucina-8B/metabolismo , Transdução de Sinais , Neoplasias Gástricas/patologia , Actinas/genética , Animais , Medula Óssea/metabolismo , Medula Óssea/patologia , Quimiocina CXCL1/genética , Quimiocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Proteínas de Fluorescência Verde , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Receptores de Interleucina-8B/genética , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/metabolismo , Microambiente TumoralRESUMO
BACKGROUND: Kimura's disease (KD; eosinophilic granuloma of soft tissue) is an inflammatory granulomatous disorder of unknown cause with eosinophilic infiltration that occurs mainly in soft tissue. KD occurs mainly in the head and neck, but development in the axillary region is very rare. CASE PRESENTATION: A 74-year-old Japanese woman was evaluated for a mass that she noted in the left axillary region. On physical examination, there was a palpable, thumb-sized, hard, elastic, freely movable mass in the left axilla. Blood tests showed elevated soluble interleukin-2 receptor (sIL-2R), normal serum immunoglobulin (Ig) G4, and elevated serum IgE. Ultrasonography of the left axilla showed multiple lymph nodes (LNs) with irregular margins in which central hyperechogenicity was lost. A systemic search by computed tomography (CT) showed no systemic lymphadenopathy or other mass-like lesions suspicious for a primary tumour other than in the left axillary LNs. Biopsy of an excised LN was performed under local anaesthesia for a definitive diagnosis. Histopathology showed various-sized lymphoid follicles, large nodular lesions with an enlarged mantle zone, multiple various-sized germinal centres in single nodules, and eosinophilic infiltration between the nodes. Immunohistochemical (IHC) staining of the germinal centres was positive for cluster of differentiation (CD) 10, positive for B-cell lymphoma (bcl)-6, and negative for bcl-2. These findings led to a diagnosis of KD. Ultrasound after 3 months of follow-up showed disappearance of the axillary lymphadenopathy. CONCLUSIONS: A very rare case of KD in the axillary LNs was described. KD has the potential to occur in any region.
Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/fisiopatologia , Axila/patologia , Linfonodos/patologia , Idoso , Feminino , Humanos , Imunoglobulina G/sangue , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: It has been reported that lysyl oxidase (LOX) is a hypoxia-responsive factor and is associated with the malignant progression of carcinoma. The aim of this study was to clarify the relationship between the epithelial-mesenchymal transition (EMT) and LOX in gastric cancer cells under hypoxia. METHODS: Two gastric cancer cell lines, OCUM-2MD3 and OCUM-12, were used in an in vitro study. The effect of LOX small interfering RNA (siRNA) on the EMT and motility of gastric cancer cells under hypoxic condition was analyzed by reverse transcription PCR, Western blot, a wound-healing assay, and an invasion assay. Correlations between LOX expression and the clinicopathological features of 544 patients with gastric carcinoma were examined immunohistochemically. RESULTS: Hypoxic conditions increased the number of polygonal or spindle-shaped cells resulting from EMT in gastric cancer cells. The EMT of cancer cells induced by hypoxia was inhibited by treatment with LOX siRNA. The number of migrating and invading gastric cancer cells in hypoxia was significantly decreased by LOX knockdown. LOX siRNA significantly increased the E-cadherin level and decreased the vimentin level of gastric cancer cells. LOX expression was significantly associated with invasion depth, tumor differentiation, lymph node metastasis, lymphatic invasion, venous invasion, and peritoneal metastasis. Multivariable analysis revealed that LOX was an independent parameter for overall survival. CONCLUSION: LOX affects the EMT of gastric cancer cells in hypoxic conditions. LOX expression is a useful prognostic factor for patients with gastric cancer.
Assuntos
Transição Epitelial-Mesenquimal , Proteína-Lisina 6-Oxidase/metabolismo , Neoplasias Gástricas/patologia , Idoso , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Metástase Linfática , Masculino , Proteína-Lisina 6-Oxidase/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Hipóxia TumoralRESUMO
Cancer-associated fibroblasts (CAFs) have been considered to play an important role for tumor progression of cancer. Solid tumors contain heterogeneous distribution of oxygen in their microenvironments. This study investigated the growth signaling of gastric cancer (GC) cells in focus on the interaction with CAFs and GC cells under normoxia and hypoxia. Four diffuse-type GC cell lines, two intestinal-type GC cell lines and three CAF cell lines were used. Cells were examined for expression of C-X-C chemokine receptor 4 (CXCR4), fibroblast growth factor receptor 2 (FGFR2) and stromal-derived factor 1 (SDF1) by RT-PCR, western blot, ELISA and immunohistochemical staining of xenografted tumors. GC cell proliferation was examined under hypoxia in the presence or absence of CAFs, a FGFR2 inhibitor, a CXCR4 inhibitor and HIF1α siRNA. Proliferation of diffuse-type GC cells, but not intestinal-type GC cells, was significantly increased by CAFs. CXCR4 expression by diffuse-type GC cells was significantly increased in hypoxia, while FGFR2 expression was decreased. CXCR4 expression was correlated with hypoxic microenvironment of xenografted tumor, but FGFR2 expression was not. FGFR2 inhibition significantly decreased the growth-stimulating activity of CAFs for diffuse-type GC cells in normoxia. In contrast, CXCR4 inhibition significantly decreased the growth-stimulating activity of CAFs in hypoxia. SDF1 production by CAFs was increased in hypoxia, while cancer cells did not produce SDF1. HIF1 siRNA significantly decreased both CXCR4 expression by diffuse-type GC cells and SDF1 production by CAFs. These findings suggest that diffuse-type GC cells might switch their driver pathways from FGFR2 signaling to SDF1/CXCR4 axis through HIF1 in hypoxic tumor microenvironments.
Assuntos
Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores CXCR4/metabolismo , Neoplasias Gástricas/metabolismo , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Proliferação de Células , Técnicas de Cocultura , Feminino , Fibroblastos/metabolismo , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , RNA Interferente Pequeno/genética , Receptores de Fatores de Crescimento/genética , Receptores de Fatores de Crescimento/metabolismo , Transdução de Sinais , Neoplasias Gástricas/patologia , Microambiente TumoralRESUMO
The antitumor activity of prostaglandin (PG) D2 has been demonstrated against some types of cancer, including gastric cancer. However, exogenous PGD2 is not useful from a clinical point of view because it is rapidly metabolized in vivo. The aim of this study was to clarify the antitumor efficacy of an alternative, PGD synthase (PGDS), on gastric cancer cells. The effects of PGD2 and PGDS on the proliferation of gastric cancer cells were examined in vivo and in vitro. The expression levels of PGD2 receptors and peroxisome proliferator-activated receptor γ (PPARγ) were evaluated by RT-PCR. The effects of a PPARγ antagonist or siPPARγ on the proliferation of cancer cells and the c-myc and cyclin D1 expression were examined in the presence or absence of PGD2 or PGDS. PPARγ was expressed in gastric cancer cell lines, but PGD2 receptors were not. PGD2 and PGDS significantly decreased the proliferation of gastric cancer cells that highly expressed PPARγ. PGDS increased the PGD2 production of gastric cancer cells. A PPARγ antagonist and siPPARγ transfection significantly suppressed the growth-inhibitory effects of PGD2 and PGDS. Expression of c-myc and cyclin D1 was significantly decreased by PGD2 ; this inhibitory effect was suppressed by PPARγ antagonist. Both PGD2 and PGDS significantly decreased subcutaneous tumor growth in vivo. Tumor volume after PGDS treatment was significantly less than PGD2 treatment. These findings suggest that PGDS and PGD2 decrease the proliferation of gastric cancer cells through PPARγ signaling. PGDS is a potentially promising therapeutic agent for gastric cancers that express PPARγ.
Assuntos
Antineoplásicos/administração & dosagem , Oxirredutases Intramoleculares/administração & dosagem , Lipocalinas/administração & dosagem , PPAR gama/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Oxirredutases Intramoleculares/farmacologia , Lipocalinas/farmacologia , Camundongos , PPAR gama/metabolismo , Prostaglandina D2/administração & dosagem , Prostaglandina D2/farmacologia , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/genética , Receptores de Prostaglandina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND Hemorrhagic cholecystitis is a rare disease which can be fatal in some cases. Hemorrhagic cholecystitis can sometimes be confused with common biliary diagnoses, as its symptoms imitate other hepatobiliary diseases. We report a case of hemorrhagic cholecystitis with hemobilia caused by the administration of anticoagulant agents. CASE REPORT A 70-year-old man was admitted with abdominal distention and pain. Ultrasound (US) and computed tomography (CT) showed a distended and wall-thickened gallbladder with hyperdense materials. Based on these findings and the laboratory data, the patient was diagnosed with acute cholecystitis with cholangitis. Because the patient's hemodynamics were stable, endoscopic retrograde cholangiopancreatography (ERCP) was performed first to improve the bile flow. The results of ERCP showed blood from the common bile duct by cannulation, which was suspected to reflect hemorrhagic cholecystitis. As the abdominal symptom and CT findings worsened on the day after ERCP, emergency laparoscopic cholecystectomy was performed. An examination of the specimen revealed ulcer formation on the mucosal side of the gallbladder. The patient was discharged 6 days after the operation without any surgical complications. CONCLUSIONS ERCP and early laparoscopic cholecystectomy were performed for a patient with hemorrhagic cholecystitis and hemobilia. Early diagnosis and treatment can lead to good outcomes in patients with hemorrhagic cholecystitis. Since the number of patients who are taking antithrombotic agents is increasing, hemorrhagic cholecystitis should be considered when any unusual imaging findings associated with cholecystitis are observed.
Assuntos
Colecistectomia Laparoscópica , Colecistite , Hemobilia , Idoso , Anticoagulantes/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica , Colecistite/induzido quimicamente , Colecistite/cirurgia , Hemobilia/etiologia , Humanos , MasculinoRESUMO
Stromal cell-derived factor 1α (SDF1α) and its receptor C-X-C chemokine receptor type 4 (CXCR4) have been reported to form an important chemokine signaling pathway. Our previous study reported that SDF1α from tumor stromal cells may stimulate the proliferation of gastric cancer (GC) cells through the CXCR4 axis in a hypoxic microenvironment. However, a limited number of studies have addressed the clinicopathological significance of the expression of SDF1α and CXCR4 in GC, particularly at hypoxic regions. Immunohistochemistry was used to investigate the expression levels of SDF1α, CXCR4 and the hypoxic marker carbonic anhydrase 9 (CA9) in 185 patients with stage II and III GC. The results demonstrated that CA9 was expressed on cancer and stromal cells in hypoxic lesions, CXCR4 was mainly expressed in cancer cells, and SDFα was mainly expressed in stromal cells. CXCR4 expression in cancer cells and SDFα expression in stromal cells were associated with the hypoxic regions with CA9 expression. The CA9 and CXCR4 expression in the cancer cells, and the SDF1α expression in the stromal cells (CA9/CXCR4/SDF1α) was significantly associated with macroscopic type 4 tumor (P=0.012) and the pattern of tumor infiltration into the surrounding tissue (P<0.001). The prognosis of the all CA9/CXCR4/SDF1α-positive patients was significantly poorer compared with that of patients with CA9-, CXCR4- or SDF1α-negative GC at Stage III (P=0.041). These results indicated that hypoxia may upregulate SDFα production in stromal cells and CXCR4 expression in cancer cells. The SDF1α/CXCR4 axis may serve an important role in the progression of GC.
RESUMO
We report a case of intraductal papillary mucinous neoplasm arising within the heterotopic pancreatic tissue which was found incidentally in the jejunum during surgery for bowel obstruction. A 54-year-old female patient was admitted to our hospital due to sudden abdominal pain. In preoperative findings, we diagnosed bowel obstruction and performed surgery. Intra-operative findings showed adhesive intestinal obstruction, we performed synechiotomy for adhesion release. During surgery, when searching the small intestine, we coincidentally found a tumor in the jejunum and partial resected the jejunum. Pathological examination revealed a 1.2 cm × 1.0 cm × 1.0 cm white yellow nodule with cystic spaces. Histological examination demonstrated heterotopic pancreatic tissue consisting of well-formed lobules of pancreatic acini and cystically dilated ducts containing intraductal papillary neoplasm. Moreover, in immunohistochemical staining, MUC5AC was diffusely expressed, but not MUC1, MUC2 and MUC6.