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1.
Anticancer Res ; 41(10): 4875-4883, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593435

RESUMO

BACKGROUND/AIM: Sunitinib continues to be administered as a first-line therapeutic agent in metastatic renal cell carcinoma (mRCC). This study aimed to examine the role of CD44 in sunitinib resistance and as a predictive marker in mRCC. MATERIALS AND METHODS: We analyzed the effect of CD44 knockdown on sunitinib resistance in RCC cell lines using WST-1 assays. CD44 expression in mRCC patients treated with first-line sunitinib was determined by immunohistochemistry. We validated the findings of this study by in silico analysis. RESULTS: CD44 knockdown increased sensitivity to sunitinib. Immunohistochemical analysis revealed that 19 (34.5%) of 55 mRCC cases were positive for CD44. CD44-positive cases were associated with poor progression-free survival (PFS) after first-line sunitinib treatment. In the JAVELIN 101 study, high CD44 expression was significantly associated with poor PFS after sunitinib but not after avelumab + axitinib therapy. CONCLUSION: CD44 is involved in sunitinib resistance and may be a promising marker for sunitinib treatment in mRCC.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Renais/mortalidade , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Receptores de Hialuronatos/metabolismo , Neoplasias Renais/mortalidade , Sunitinibe/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Seguimentos , Humanos , Receptores de Hialuronatos/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas
2.
Artigo em Inglês | MEDLINE | ID: mdl-34597393

RESUMO

The multilocular thymic cyst (MTC) is a rare, acquired disease caused by inflammatory changes in the thymus, and is associated with autoimmune diseases. We report a case of MTC with thrombocytopaenia, which improved following surgical resection. A 45-year-old man developed thrombocytopaenia with an anterior mediastinal tumour. Thrombocytopaenia due to an autoimmune mechanism, associated with thymoma or thymus-related disease, was suspected. Pathologic analysis following thoracoscopic thymectomy confirmed MTC. The platelet level recovered postoperatively. Our findings suggested a relationship between the acquired formation of MTC and the development of autoimmune antibodies. However, further investigation is needed to obtain more information.

3.
Cancer Cytopathol ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478237

RESUMO

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a risk-stratification reporting system that was introduced in 2018. The objective of this multi-institutional study was to evaluate the utility of the MSRSGC in Japan. METHODS: In total, 1608 fine-needle aspiration samples with matching histologic diagnoses were retrieved from 12 large institutions in Japan. The diagnostic categories of the MSRSGC were assigned prospectively or retrospectively, and the results were compared with the histologic diagnoses. RESULTS: The cases were classified as follows: nondiagnostic, 18.1%; non-neoplastic, 4.1%; atypia of undetermined significance, 11.5%; neoplasm-benign, 43.7%; salivary gland neoplasm of uncertain malignant potential, 9.6%; suspicious for malignancy, 3.6%; and malignant, 9.4%. The risk of neoplasm and the risk of malignancy in each MSRSGC category were as follows: nondiagnostic, 72.9% and 13.4%, respectively; non-neoplastic, 15.2% and 9.1%, respectively; atypia of undetermined significance, 77.9% and 24.9%, respectively; neoplasm-benign, 99% and 1.8%, respectively; salivary gland neoplasm of uncertain malignant potential, 94.8% and 37%, respectively; suspicious for malignancy, 100% and 89.7%, respectively; and malignant, 100% and 99.3%, respectively. The accuracy of the MSRSGC for diagnosing neoplasms was 97.8%, and its accuracy for diagnosing malignancy was 97.3%. Institutions that used Romanowsky-stained preparations had lower nondiagnostic rates and lower risks of neoplasm and malignancy in the non-neoplastic category. CONCLUSIONS: The MSRSGC is useful for risk stratification and quality control. Widespread use of the MSRSGC would improve the accuracy of salivary gland cytology and lead to better patient care in Japan.

4.
Anticancer Res ; 41(9): 4287-4294, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475048

RESUMO

BACKGROUND/AIM: Sunitinib continues to be administered as a first-line therapeutic agent in metastatic renal cell carcinoma (mRCC). This study examined the potential role of p53 in sunitinib resistance and as a predictive marker in mRCC. MATERIALS AND METHODS: We analysed the effects of p53 knockout on sunitinib resistance. p53 expression in 53 mRCC patients receiving first-line sunitinib was determined immunohistochemically. We performed in silico analysis to examine the predictive value of p53 in mRCC. RESULTS: WST-1 assays showed that p53 knockout decreased sensitivity to sunitinib. Sunitinib and nutlin-3 together suppressed cell growth. Immunohistochemistry revealed 11 p53-positive cases among 53 patients with mRCC. Kaplan-Meier analysis showed that p53-positive cases tended to be associated with poor progression-free survival (PFS) after first-line sunitinib treatment. In the JAVELIN 101 study, TP53 mutation was significantly associated with poor PFS after sunitinib treatment. CONCLUSION: p53 may be involved in sunitinib resistance and represent a valuable marker for sunitinib treatment in mRCC.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Imidazóis/farmacologia , Neoplasias Renais/tratamento farmacológico , Piperazinas/farmacologia , Sunitinibe/farmacologia , Proteína Supressora de Tumor p53/genética , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Sinergismo Farmacológico , Feminino , Técnicas de Inativação de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos
5.
Kyobu Geka ; 74(9): 720-723, 2021 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-34446630

RESUMO

Primary mediastinal leiomyosarcoma is extremely rare, and few reports in the literature have described the clinical features of this malignancy. We report a case of a small anterior mediastinal leiomyosarcoma that showed rapid growth within a short period. An 85-year-old woman showed a small anterior mediastinal tumor on chest computed tomography (CT), three months prior to presentation. Contrast-enhanced chest CT revealed rapid tumor growth, and positron emission tomography/CT revealed significant 18-fluorodeoxyglucose uptake, suggestive of malignancy. Thoracoscopic tumor resection was performed via the left thoracic approach. In addition to the tumor and surrounding anterior mediastinal tissue, we resected an area of pericardial infiltration. The tumor was diagnosed as a primary mediastinal leiomyosarcoma based on histopathological and immunohistochemical findings.


Assuntos
Leiomiossarcoma , Neoplasias do Mediastino , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Humanos , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/cirurgia , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/cirurgia , Mediastino/diagnóstico por imagem , Mediastino/cirurgia , Tomografia Computadorizada por Raios X
6.
J Gastrointest Surg ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379296

RESUMO

BACKGROUND: Transmembrane serine protease 4 (TMPRSS4) belongs to the family of type II transmembrane serine proteases that are known to be upregulated in many malignant tumors. However, there is a paucity of studies documenting the clinical impact and biological effects of TMPRSS4 on gastric cancer (GC) patients who underwent surgery. METHODS: Tissues samples were obtained from 105 patients with GC who underwent gastrectomy followed by adjuvant chemotherapy, excluding those at stage I. The expression of TMPRSS4 was examined through immunohistochemical analysis. The association between TMPRSS4 expression and clinico-pathological features as well as prognosis was assessed. Moreover, the effects of TMPRSS4 expression on cell migration and sensitivity to 5-FU were investigated. RESULTS: The expression rate of TMPRSS4 was 56.3% (59/105) in GC cases. The expression of TMPRSS4 was positively correlated with the depth of tumor (T) and venous (V) invasion. The 5-year overall survival (OS) and recurrence-free survival (RFS) rates of the TMPRSS4-positive group was significantly lower than that of the TMPRSS4-negative group (p=0.0001 and p=0.005, respectively). Especially, there was significant differences in OS and RFS of patients with stage III cancer between the two groups (p=0.0064 and 0.012, respectively). Multivariate analysis demonstrated that TMPRSS4 expression and the stage of cancer were crucial prognostic factors for RFS. TMPRSS4-silenced GC cells exhibited increased sensitivity to 5-FU when compared with the non-specific control siRNA-transfected cells. CONCLUSION: TMPRSS4 can be considered as a potential prognostic biomarker, especially for stage III, and a promising therapeutic target for GC.

7.
Anticancer Res ; 41(7): 3673-3682, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230166

RESUMO

AIM: This study aimed to investigate useful prognostic factors of immunotherapy in patients with lung cancer. PATIENTS AND METHODS: We retrospectively observed 73 patients who underwent immunotherapy (nivolumab, pembrolizumab, and atezolizumab) for lung cancer. The systemic inflammatory score (SIS) was calculated as the sum of the following factors scored one point each: Hemoglobin <12.5 g/dl and serum albumin <3.6 g/dl, resulting in scores of 0-2. We examined the correlation between the SIS and initial tumor response and progression-free and overall survival with other existing markers, namely tumor programmed death-ligand 1 (PD-L1) expression level; neutrophil-to-lymphocyte ratio (NLR); modified Glasgow prognostic score; and prognostic nutritional index, etc. Results: SIS ≤1 was significantly associated with better initial tumor response. In multivariate analysis, PD-L1 expression ≥50% (p=0.010), SIS ≤1 (p=0.028) and NLR <5.6 (p=0.047) were significantly associated with longer progression-free survival, and SIS ≤1 (p=0.030) and NLR <5.6 (p=0.037) were associated with longer overall survival. CONCLUSION: SIS is a useful marker of the efficacy of immunotherapy that can be obtained via routine blood tests.


Assuntos
Inflamação/patologia , Neoplasias Pulmonares/patologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neutrófilos/patologia , Nivolumabe/uso terapêutico , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
8.
Neuropathology ; 41(4): 266-272, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33942396

RESUMO

Immune-related adverse events (irAEs) commonly involve the gastrointestinal tract, endocrine glands, skin, and liver, and rarely the nervous system. The pathomechanism of irAEs in the nervous system is unclear, and so characterizing these severe toxic effects is a priority, even if irAEs are uncommon in the nervous system. Our patient presented subacute muscle weakness and dysesthesia with colitis as irAEs caused by pembrolizumab, one of the anti-programmed death-1 (PD-1) antibodies. Electromyography revealed abundant fibrillations and fasciculations of upper and lower extremities and severe reduction in motor unit potentials; however, antineutrophil cytoplasmic antibodies, rheumatoid factor, autoantibodies against Hu and Yo, and anti-ganglioside antibodies, such as GQ1b, were undetectable in the serum. Although he was treated with high-dose glucocorticoids, antibiotics, and a monoclonal anti-tumor necrosis factor alpha (TNFα) antibody, he developed colonic perforation. The total colorectal resection was performed, and the resected colon showed mucosal defect and perforation. He died of lung aspergillosis. Postmortem examination revealed CD8-positive lymphocyte infiltration around neurons of dorsal root ganglia. The sciatic nerve displayed the widening of myelin laminae and thinning of myelinated fibers but not a decrease in the density of myelinated nerve fibers. In the sural nerve, the density of myelinated fibers slightly decreased, and some fibers showed less densely myelinated laminae. Drug safety information, including previous randomized trials of anti-PD-1 and anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibodies, showed that patients treated with anti-PD-1 antibodies appeared to have more frequent and severe peripheral neuropathies compared to those in patients who received anti-CTLA-4 antibodies (1.59% vs. 0.69%; Fisher exact test, P < 0.001; three severe events vs. zero severe events). The present results and drug safety information suggest that the pathomechanism of irAEs caused by anti-PD-1 antibodies is different from that by anti-CTLA-4 antibodies. The neurological irAEs might be clues to solving the pathomechanism of irAEs.

9.
PLoS One ; 16(5): e0241454, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34014970

RESUMO

The current understanding of clinicopathological features and genomic variants of small-bowel cancer is limited, in part due to the rarity of the disease. However, understanding of these factors is necessary for the development of novel therapeutic agents for small-bowel cancer. Thus, we aimed to identify the clinicopathological features and genomic variants associated with its prognosis and recurrence. We retrospectively examined 24 consecutive patients with primary small-bowel cancer surgically treated between May 2005 and August 2018 and collected 29 tumor specimens. The 29 lesions were subjected to mismatch repair status evaluation, using immunohistochemistry (IHC), and targeted genomic sequencing, after which they were analyzed using a panel of 90 cancer-related genes. IHC revealed that 45% (13/29) of the lesions exhibited deficient mismatch repair. The most common genomic variants in small-bowel cancers were in TP53 (48%, 13/27), followed by KRAS (44%, 12/27), ARID1A (33%, 9/27), PIK3CA (26%, 7/27), APC (26%, 7/27), and SMAD4, NOTCH3, CREBBP, PTCH1, and EP300 (22%, 6/27 each). Overall survival and disease-specific survival of patients with tumor mutational burden (TMB) ≥10 mutations/Mb (n = 17) were significantly better than those of patients with TMB <10 mutations/Mb (n = 6). Additionally, patients with a mutant SMAD4 had poorer recurrence-free survival than those with wild-type SMAD4. Our results suggested that TMB and SMAD4 mutations were associated with the prognosis of small-bowel cancer patients. Thus, cancer genomic analysis could be useful in the search for biomarkers of prognosis prediction in small-bowel cancers.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Íleo/genética , Neoplasias do Jejuno/genética , Mutação , Adulto , Idoso , Proteína de Ligação a CREB/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Neoplasias do Íleo/patologia , Neoplasias do Jejuno/patologia , Masculino , Pessoa de Meia-Idade , Receptores Notch/genética , Proteínas Smad/genética , Análise de Sobrevida , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genética , Proteínas ras/genética
10.
Oncol Rep ; 45(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33907853

RESUMO

Tumor­stroma interactions serve a crucial role in the development of colorectal cancer (CRC), in which secreted protein acidic and rich in cysteine (SPARC) has been implicated. Due to interactions between cancer and stromal cells [mesenchymal stem cells (MSCs)], SPARC gene expression is markedly upregulated in CRC cells. The present study investigated the role of SPARC in CRC development and its potential as a biomarker. Specifically, the present study examined the association between SPARC expression and clinicopathological characteristics in 42 cases of CRC. SPARC expression in cancer cells was associated with T grade, N grade (TNM classification), stage and poor prognosis. Furthermore, the area of fibroblast­activating protein­positive staining around the cancer cells was increased in SPARC­positive compared with SPARC­negative cases. Proliferation and wound healing assays in SPARC­silenced KM12SM cells [short hairpin RNA SPARC (shSPARC)], the reduced SPARC expression of which was demonstrated by reverse transcription­quantitative PCR, revealed that the proliferative and migratory capacity of shSPARC cells did not differ from that of wild­type (WT) cells. However, it was markedly reduced when co­cultured with MSCs. Furthermore, in vivo, immunohistological analysis and RNA sequencing were conducted in an orthotopic implanted mouse model. Tumor growth and lymph node metastasis were markedly suppressed in shSPARC­transplanted tumors compared with WT­transplanted tumors, with a more marked suppression observed following shSPARC co­transplantation with MSCs. Immunohistological examination further revealed that the stromal reaction and epithelial­mesenchymal transition (EMT) were markedly suppressed in tumors co­transplanted with shSPARC and MSCs, and these results were consistent with RNA sequencing using RNA extracted from orthotopic tumors. Overall, these results suggested that SPARC expression in CRC cells is dependent on the interaction between cancer cells and stromal cells to induce EMT and promote stromal formation in the tumor microenvironment, suggesting its suitability as a novel target molecule for CRC treatment.

11.
BMC Gastroenterol ; 21(1): 162, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849435

RESUMO

BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a new disease concept defined by the World Health Organization in 2010. ITPN progresses with tubulopapillary growth in the pancreatic duct and is known to have a fair prognosis. Localization in the main pancreatic duct (MPD) is one characteristic. There are few case reports of ITPN in a branch of the pancreatic duct (BD). CASE PRESENTATION: We encountered a case of ITPN localized in BD. An 85-year-old man was followed after colonic surgery for rectal carcinoma. An abdominal computed tomography scan revealed a cystic mass in the pancreatic head and further examination was done. A T2 weighted intension picture in magnetic resonance imaging showed a 20 mm cystic lesion with an internal mass of 15 mm. Duodenal papilla were slightly open and endoscopic retrograde pancreatography revealed mild and diffuse dilatation of the main pancreatic duct and mucin in the MPD. In consideration with the image examinations, we diagnosed the tumor as an intraductal papillary mucinous neoplasm with carcinoma because of its large mural nodule (> 10 mm in size) in a cyst. Consequently, a pancreaticoduodenectomy was performed. Macroscopically, a white solid tumor sized 2.5 × 1.8 × 1.0 was identified in the head of the pancreas. The cut surface of the resected pancreas showed a side-branch type intraductal tumor with tubulopapillary architecture without mucin secretion. Immunohistochemical staining was positive for MUC1, and negative for MUC2 and MUC5AC. The final diagnosis was determined to be pancreatic ITPN from BD. At the time of this report (48 months post-surgery), the patient remains disease-free without evidence of recurrence. CONCLUSION: ITPNs localized in BD are rare and diagnosis prior to surgery is difficult. In our case, the shape was round, not papillary, and with little fluid. These characteristics are different from a branch duct type IPMN and can be a clue to suspect ITPN in BD.


Assuntos
Carcinoma Ductal Pancreático , Carcinoma Papilar , Neoplasias Pancreáticas , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Papilar/cirurgia , Humanos , Masculino , Recidiva Local de Neoplasia , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia
12.
Br J Cancer ; 125(1): 65-77, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33785877

RESUMO

BACKGROUND: Although unresectable or recurrent gastric cancers (GC) are frequently treated with platinum-based chemotherapy, response to treatment remains unpredictable. Because Schlafen 11 (SLFN11) is recently identified as a critical determinant of platinum sensitivity, we investigated the potential clinical utility of SLFN11 in the treatment of GC. METHODS: We analysed the correlation between SLFN11 expression and overall survival in 169 GC patients by our established immunohistochemical approach. The impact of SLFN11 expression on the response to platinum and transition of SLFN11 expression upon long-term treatment with platinum were examined using GC cell lines and organoids. RESULTS: GC patients with high-SLFN11 expression exhibited significantly better survival than those with low-SLFN11 expression, and the significance increased when we selected patients treated with platinum-based chemotherapy. Knockout of SLFN11 and reactivation of SLFN11 in GC cells conferred resistance and sensitivity to platinum, respectively. In GC cells and organoids, long-term treatment with oxaliplatin suppressed SLFN11 expression while imparting drug resistance. The acquired resistance to oxaliplatin was reversed by reactivation of SLFN11 with epigenetic modifying drugs. CONCLUSIONS: This is the first report revealing definitive clinical implications of SLFN11 in the treatment of GC patients and providing novel strategies for the drug selection based on SLFN11 expression.

13.
Int J Surg Case Rep ; 81: 105727, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33714895

RESUMO

INTRODUCTION: Neoadjuvant imatinib for large GISTs may prevent tumor rupture and the need for extended surgery by reducing tumor size. In this study, we present a case of large gastric GIST with diaphragm invasion, due to the patient receiving laparoscopic resection following preoperative imatinib treatment. PRESENTATION OF CASE: A 72-year-old woman was hospitalized with left hypochondriac pain for a month. Examinations revealed a large heterogeneous gastric mass measuring 80 mm in size, arising from the greater curvature of the corpus. The mass invaded the left thoracic diaphragm. Treatment with imatinib at an initial dosage of 400 mg/day was initiated. After a further two months of follow-up, the lesion had sustained reduction to 50 mm in size, however, the invasion to the diaphragm remained. The patient eventually underwent laparoscopic partial gastrectomy and partial resection of the diaphragm with curative intent. Adjuvant chemotherapy was initiated at one month after the surgery, however, was discontinued due to nausea. After one-year follow-up, no recurrence was noted. DISCUSSION: Neoadjuvant imatinib may shrink tumor size remarkably and prevent tumor rupture during surgery, and thus lead to increased rates of complete resection. To date, several publications have directly compared the oncologic results between laparoscopic and open resection for GISTs. In the present case, the tumor was movable, and moderately fixed on diaphragm. It was favorable condition for laparoscopic surgery. CONCLUSIONS: This is the first report of a large gastric GIST invading the diaphragm that was successfully treated by laparoscopic resection after tumor reduction by neoadjuvant imatinib.

14.
Anticancer Res ; 41(3): 1349-1355, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788726

RESUMO

BACKGROUND/AIM: Small bowel adenocarcinoma (SBA) is a relatively rare malignant epithelial neoplasm. Thus, little is known about prognostic biomarkers of SBA. Annexin A10 (ANXA10) is a member of the annexin family. The significance of ANXA10 expression in SBA is unclear. This is the first study to examine the expression of ANXA10 in SBA. MATERIALS AND METHODS: We immunohistochemically evaluated ANXA10 expression of SBA and studied the relationship between ANXA10 expression and clinicopathological factors. RESULTS: ANXA10 expression was detected in 17 (56.7%) of 30 SBA cases and was significantly associated with poor overall survival. Univariate predictors for poor prognosis were tumour size (p=0.017) and ANXA10 expression (p=0.026). In multivariate analysis, ANXA10 expression (p=0.038) and tumour size (p=0.024) were found to be independent predictors of poor prognosis. CONCLUSION: ANXA10 could be a new prognostic biomarker for SBA.


Assuntos
Adenocarcinoma/metabolismo , Anexinas/biossíntese , Biomarcadores Tumorais/biossíntese , Intestino Delgado/metabolismo , Adenocarcinoma/diagnóstico , Idoso , Feminino , Humanos , Imuno-Histoquímica/métodos , Intestino Delgado/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
Int J Colorectal Dis ; 36(5): 949-958, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33150491

RESUMO

PURPOSE: The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines indicate lymphovascular invasion-evaluated by hematoxylin and eosin (HE) staining-as a surgical requirement after endoscopic submucosal dissection (ESD) in T1 colorectal carcinoma (CRC) patients; however, immunohistochemical evaluation may be superior. This study aimed to clarify the significance of immunohistochemical lymphovascular evaluation as an indicator for additional surgery of T1 CRC after ESD, and assessed the guidelines' adequacy, even when evaluating through immunostaining. METHODS: Patients with T1 CRC who underwent ESD were enrolled across three institutions between January 2012 and December 2017. Immunohistochemical lymphovascular evaluation was performed. Clinicopathological features, pathological evaluations, and surgery indications were recorded. Univariate and multivariate logistic regression identified risk factors for lymph node (LN) metastasis of T1 CRC after ESD. RESULTS: Among 370 patients with T1 CRC, recurrence, 5-year overall survival, and 5-year disease specific survival rates were 1.6%, 94.6%, and 99.5%, respectively. Six patients (1.6%) experienced recurrence, five of whom underwent additional surgery. Those with no risk factors did not exhibit recurrence. A total of 215 (58.1%) patients underwent additional surgery after ESD, 21 (9.7%) of whom exhibited LN metastasis. Among 16 patients who underwent additional surgery due to lymphovascular invasion, three (18.8%) had LN metastasis. Multivariate logistic regression analysis identified lymphatic invasion as a significant risk factor for LN metastasis (odds ratio 3.9, 95% confidence interval 1.0-14.6, P = 0.0421). CONCLUSIONS: The JSCCR guidelines have clinical validity, and immunohistochemical lymphatic evaluation findings potentially predict LN metastasis for T1 CRC after ESD.


Assuntos
Carcinoma , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Neoplasias Colorretais/cirurgia , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
18.
Virchows Arch ; 478(3): 569-579, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32474729

RESUMO

DNA-damaging agents include first-line drugs such as platinum (cisplatin, carboplatin), topoisomerase inhibitors (etoposide, doxorubicin), and replication inhibitors (cytarabine, gemcitabine). Despite their wide and long usage, there is no clinically available biomarker to predict responses to these drugs. Schlafen 11 (SLFN11), a putative DNA/RNA helicase, recently emerged as a dominant determinant of sensitivity to these drugs by enforcing the replication block in response to DNA damage. Since the clinical importance of SLFN11 is implicated, a comprehensive analysis of SLFN11 expression across human organs will provide a practical resource to develop the utility of SLFN11 in the clinic. In this study, we established a scoring system of SLFN11 expression by immunohistochemistry (IHC) and assessed SLFN11 expression in ~ 700 malignant as well as the adjacent non-tumor tissues across 16 major human adult organs. We found that the SLFN11 expression is tissue specific and varies during tumorigenesis. Although The Cancer Genome Atlas (TCGA) is a prevailing tool to assess gene expression in various malignant and normal tissues, our IHC data exhibited obvious discrepancy from the TCGA data in several organs. Importantly, SLFN11-negative tumors, potentially non-responders to DNA-damaging agents, were largely overrated in TCGA because TCGA samples are a mixture of infiltrating immune cells, including T cells, B cells, and macrophages, which have strong SLFN11 expression. Thus, our study reveals the significance of immunohistochemical procedures for evaluating expression of SLFN11 in patient samples and provides a robust resource of SLFN11 expression across adult human organs.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Dano ao DNA , Resistencia a Medicamentos Antineoplásicos , Imuno-Histoquímica , Neoplasias/enzimologia , Proteínas Nucleares/análise , RNA-Seq , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Tomada de Decisão Clínica , Bases de Dados Genéticas , Feminino , Humanos , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Proteínas Nucleares/genética , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
19.
Cancer Lett ; 498: 111-120, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129954

RESUMO

Despite recent advances in cancer immunotherapy, the efficacy of colorectal cancer (CRC) immunotherapy regimens is limited. This study evaluated the combined effect of an anti-PD-1 antibody and a platelet-derived growth factor receptor inhibitor (imatinib) on CRC progression using an orthotopic transplanted mouse model that reproduced the three histological phenotypes of CRC (inflamed-, excluded-, and desert-type). The frequency of each of these phenotypes in 196 human CRC tissue samples was also evaluated. Excluded-type CRC had the highest frequency in human tissue samples. In the mouse model, imatinib suppressed stromal reaction and increased sensitivity to anti-PD-1 treatment in excluded-type CRC. Antitumor effect was observed in mice with excluded-type tumors only after concomitant administration of anti-PD-1 antibody and imatinib. Immunohistological analysis revealed a reduction in stromal volume and an increase in the number of CD8-positive T cells in the tumor nest following combination therapy. RNA sequencing revealed significant activation of immune-related pathways and suppression of stromal-related pathways in transplanted tumors treated with combination therapy compared with tumors treated with anti-PD-1 antibody monotherapy. This combination therapy may prove effective for CRC cases that are unresponsive to anti-PD-1 antibody monotherapy.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Idoso , Animais , Anticorpos/farmacologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Mesilato de Imatinib/farmacologia , Imunoterapia/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Receptor de Morte Celular Programada 1/metabolismo , Estudos Retrospectivos
20.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33317925

RESUMO

We report a case of gamma knife surgery (GKS)-induced chronic encapsulated expanding hematoma with extensive literature review. A 17-year-old young man underwent GKS after embolization for arteriovenous malformation (AVM) in the right frontal lobe and the AVM completely disappeared. He developed a generalized convulsion 15 years after GKS. MRI showed a small oedematous change at the AVM site. His epileptic seizure was controlled with anticonvulsant. His epilepsy recurred after three years, and MRI revealed an intracerebral hematoma with extensive surrounding edema at the same lesion. He underwent cerebral angiography and a recurrence of AVM was prevented. The hematoma was surgically removed, and intraoperative finding confirmed an old hematoma with a capsule and capillary hyperplasia, without developing cavernous angioma. The final diagnosis was a secondary chronic encapsulated expanding hematoma after GKS. This is the first report to show the early-stage imaging findings of this late effect after GKS.

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