ABSTRACT
The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Medical Oncology , Immunotherapy , Neoadjuvant Therapy , ChinaABSTRACT
BACKGROUND: The widespread use of chemical insecticides has resulted in the development of resistance in German cockroaches worldwide, and biopesticides based on entomopathogenic fungi as active ingredients have become a promising alternative strategy. Resistance can change many of the physiological and biochemical characteristics of insect pests, such as cuticle thickness, detoxification enzyme activity, and even intestinal flora composition. Thus, potential interactions between pathogenic fungi and insecticide resistance may lead to unpredictable changes in pest susceptibility to fungi. RESULTS: Beta-cypermethrin-resistant German cockroaches were more susceptible to infection with the fungus Metarhizium anisopliae regardless of age and sex. Histopathological results showed that the infection of resistant strains (R) by M. anisopliae was visibly faster than that of susceptible strains (S). The gut microbiota of the S strain indicated a stronger ability to inhibit fungi in vitro. The abundance of Parabacteroides, Lachnoclostridium, and Tyzzerella_3 decreased significantly in the R strain, and most demonstrated the ability to regulate glucose and lipid metabolism, and antifungal infections. The expression levels of Akirin, BgTPS, and BgPo genes in the R strain were significantly lower than those in the S strain, while BgChi and CYP4G19 gene expression were significantly higher. The mortality of cockroaches infected with M. anisopliae decreased to varying degrees after RNA interference, reflecting the role of these genes in antifungal infection. CONCLUSIONS: Results confirmed that insecticide resistance may enhance cockroach susceptibility to fungi by altering intestinal flora and gene expression. Fungal biopesticides have high utilization value in pest control and insecticide resistance management strategies. © 2021 Society of Chemical Industry.
Subject(s)
Blattellidae , Metarhizium , Pyrethrins , Animals , Blattellidae/genetics , Blattellidae/microbiology , Insecticide Resistance/genetics , Metarhizium/genetics , Pyrethrins/pharmacologyABSTRACT
BACKGROUND: Approximately 10% of patients with gastric cancer (GC) have a genetic predisposition toward the disease. However, there is scant knowledge regarding germline mutations in predisposing genes in the Chinese GC population. This study aimed to determine the spectrum and distribution of predisposing gene mutations among Chinese GC patients known to have hereditary high-risk factors for cancer. METHODS: A total of 40 GC patients from 40 families were recruited from seven medical institutions in China. Next-generation sequencing was performed on 171 genes associated with cancer predisposition. For probands carrying pathogenic/likely pathogenic germline variants, Sanger sequencing was applied to validate the variants in the probands as well as their relatives. RESULTS: According to sequencing results, 25.0% (10/40) of the patients carried a combined total of 10 pathogenic or likely pathogenic germline variants involving nine different genes: CDH1 (n = 1), MLH1 (n = 1), MSH2 (n = 1), CHEK2 (n = 1), BLM (n = 1), EXT2 (n = 1), PALB2 (n = 1), ERCC2 (n = 1), and SPINK1 (n = 2). In addition, 129 variants of uncertain significance were identified in 27 patients. CONCLUSIONS: This study indicates that approximately one in every four Chinese GC patients with hereditary high risk factors may harbor pathogenic/likely pathogenic germline alterations in cancer-susceptibility genes. The results further indicate a unique genetic background for GC among Chinese patients.
ABSTRACT
RATIONALE: Follicular dendritic cell (FDC) sarcoma is a rare tumor with FDC differentiation that typically arises within lymph nodes but can also occur extranodally. To date, the primary esophageal FDC sarcoma has not been reported in the English literature. PATIENT CONCERNS: We described a 67-year-old female who foremostly presented with dysphagia, and the patient was readmitted due to a dry cough and pain of his right shoulder 2 years after initial treatment. DIAGNOSES: Primary esophageal FDC sarcoma with the right superior mediastinal lymph node metastasis. INTERVENTIONS: The esophageal tumor was removed by endoscopic submucosal dissection at the first hospitalization. At the second hospitalization 2 years after the initial visit, the tracheal stent loaded with (125) iodine radioactive seeds was placed. The profiles of genetic variations and immunotherapeutic biomarkers were also explored by next-generation sequencing protocol from the patient's blood, esophageal primary, and mediastinal metastatic tumor samples. OUTCOMES: The patient's symptom transitorily relieved, but she gave up further treatment and died 2 months after the tracheal stent was placed. As for the genomic alterations, we found 9 gene mutations in all the samples, including checkpoint kinase 2(CHEK2), FAT atypical cadherin 1 (FAT1), tumor protein 53 (TP53), DPYD, ERBB2 interacting protein (ERBB2IP), FBXW7, KMT2D, PPP2R1A, TSC2, whereas amplification of MYC was only in the metastatic example. The analysis of clonal evolution and phylogenetic tree showed the propagation and replay of polyclonal esophageal FDC sarcoma. At the same time, the detection of biomarkers for immunotherapy revealed microsatellite stable and mismatch repair-proficient (pMMR), which predicted a relatively poor anti-programmed death (PD-1)/programmed death ligand (PD-L1) immunotherapy outcome. On the contrary, the tumor mutational burdens were 10 mutations per 1 million bases in both the primary and metastatic tumor sample, which ranked the top 23.3% in solid tumors mutational burdens database of Geneseeq and might be a good predictor of the efficacy of anti-PD-1/PD-L1 immunotherapy. LESSONS: To the best of our knowledge, this case report announced the first case of extranodal primary esophageal FDC sarcoma in the world, and firstly revealed its unique genetic alterations profiles, which might contribute to further in-depth study of this rare disease.
Subject(s)
Dendritic Cell Sarcoma, Follicular/genetics , Esophageal Neoplasms/genetics , Lymphatic Metastasis/genetics , Aged , Biomarkers, Tumor/genetics , Dendritic Cell Sarcoma, Follicular/diagnostic imaging , Dendritic Cell Sarcoma, Follicular/therapy , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/therapy , Fatal Outcome , Female , Humans , Mutation , Positron Emission Tomography Computed Tomography , Treatment RefusalABSTRACT
How to induce immune tolerance without long-term need for immunosuppressive drugs has always been a central problem in solid organ transplantation. Modulating immunoregulatory cells represents a potential target to resolve this problem. Myeloid-derived suppressor cells (MDSCs) are novel key immunoregulatory cells in the context of tumor development or transplantation, and can be generated in vitro. However, none of current systems for in vitro differentiation of MDSCs have successfully achieved long-term immune tolerance. Herein, we combined dexamethasone (Dex), which is a classic immune regulatory drug in the clinic, with common MDSCs inducing cytokine granulocyte macrophage colony stimulating factor (GM-CSF) to generate MDSCs in vitro. Addition of Dex into GM-CSF system specifically increased the number of CD11b+ Gr-1int/low MDSCs with an enhanced immunosuppressive function in vitro. Adoptive transfer of these MDSCs significantly prolonged heart allograft survival and also favored the expansion of regulatory T cells in vivo. Mechanistic studies showed that inducible nitric oxide sythase (iNOS) signaling was required for MDSCs in the control of T-cell response and glucocorticoid receptor (GR) signaling played a critical role in the recruitment of transferred MDSCs into allograft through upregulating CXCR2 expression on MDSCs. Blockade of GR signaling with its specific inhibitor or genetic deletion of iNOS reversed the protective effect of Dex-induced MDSCs on allograft rejection. Together, our results indicated that co-application of Dex and GM-CSF may be a new and important strategy for the induction of potent MDSCs to achieve immune tolerance in organ transplantation.
Subject(s)
Dexamethasone/pharmacology , Myeloid-Derived Suppressor Cells/immunology , Transplantation Immunology/immunology , Adoptive Transfer , Allografts/immunology , Animals , Cell Differentiation/drug effects , Cell Differentiation/immunology , Glucocorticoids/pharmacology , Graft Rejection/immunology , Graft Rejection/prevention & control , Graft Survival/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Heart Transplantation , Immunotherapy , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Myeloid-Derived Suppressor Cells/cytology , Myeloid-Derived Suppressor Cells/metabolism , Nitric Oxide Synthase Type II/immunology , Nitric Oxide Synthase Type II/metabolism , Receptors, Glucocorticoid/immunology , Receptors, Glucocorticoid/metabolismABSTRACT
There are two commonly accepted methods for detecting microsatellite status. One is to detect amplified microsatellite loci by polymerase chain reaction (PCR) and the other is to detect mismatch repair gene (MMR) protein expression by immunohistochemistry (IHC). PCR detection is considered to be accurate in clinical operations while IHC is widely used due to ease of operation and lesser expense. In order to compare IHC with PCR in detecting microsatellite status in colorectal carcinoma, a total of 569 samples of colorectal carcinoma resection were collected in the Department of Pathology, Nanjing Drum Tower Hospital, between June 2014 and June 2017. In all samples, IHC and PCR was used to detect microsatellite status and the consistency of results between the two methods was compared. We found that 48 cases of microsatellite instability (MSI) were detected by PCR including 37 cases of microsatellite instability high (MSI-H), 11 cases of microsatellite instability low (MSI-L), and 521 cases of MSS. MSI accounted for 8.44% of all cases and MSI-H accounted for 6.50%. IHC results of the 569 patients showed that 69 cases were deficient mismatch repair (dMMR) and 500 cases were proficient mismatch repair (pMMR). dMMR accounted for 12.13% of all cases. Loss expression of PMS2 protein was the most common while MSH6 was rare. The coincidence rate of the two methods for detecting microsatellite states was 91.92%. IHC and the PCR method had high consistency in microsatellite status. Compared with PCR, the IHC method is more economical and more convenient for clinical operations. When the 4 repair proteins were without deficiency detected by IHC, it could be diagnosed as MSS/MSI-L and further PCR was not necessary. When any repair protein was found to be deficient, PCR detection was needed to determine whether MSI existed. Our conclusion will save a lot of time and costs in clinical work.
ABSTRACT
Genetic engineering has resulted in more than 50 recombinant bispecific antibody formats over the past two decades. Bispecific scFv antibodies represent a successful and promising immunotherapy platform that retargets cytotoxic T cells to tumor cells, with one scFv directed to tumor-associated antigens and the other to T cells. Based on this antibody construct, strategies for both specific tumor targeting and T cell activation are reviewed here. Three distinct types of tumor antigens are considered to optimize specificity and safety in bispecific scFv based treatment: cancer-testis antigens, neo-antigens and virus-associated antigens. In terms of T cell activation, although CD3 has been widely applied in bispecific scFvs being developed, CD28 and CD137 among co-stimulatory signals are also ideal candidates to be evaluated. Besides, LIGHT and HIV-Tat101 have drawn much attention as their potential roles in modulating antitumor responses.
ABSTRACT
AIM: To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination (PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma (HCC). METHODS: A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases (the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL. RESULTS: Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response (PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade II bone marrow suppression and the remaining patients had no significant hematological side effects. CONCLUSION: Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.
Subject(s)
Bone Neoplasms/therapy , Cancer Vaccines/therapeutic use , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Lung Neoplasms/therapy , Peptides/therapeutic use , Peritoneal Neoplasms/therapy , Precision Medicine/methods , Vaccination/methods , Adult , Aged , Bone Marrow/drug effects , Bone Neoplasms/blood , Bone Neoplasms/secondary , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/pathology , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Female , Humans , Liver Neoplasms/blood , Liver Neoplasms/pathology , Lung Neoplasms/blood , Lung Neoplasms/secondary , Male , Middle Aged , Neoplasm Staging , Peritoneal Neoplasms/blood , Peritoneal Neoplasms/secondary , Portal Vein/pathology , Precision Medicine/adverse effects , Radiotherapy/adverse effects , Radiotherapy/methods , Vaccination/adverse effects , Venous Thrombosis/etiology , Venous Thrombosis/therapy , alpha-Fetoproteins/analysisABSTRACT
Colorectal cancers (CRCs) exhibiting microsatellite instability (MSI) have special biological behavior. The clinical predictors for MSI and its survival relevance for the Chinese population were still unclear. Seven hundred ninety-five CRC patients were retrospectively assessed. Mismatch repair (MMR) proteins (MSH2, MSH6, PMS1, and MLH1) expression was detected by immunohistochemistry using tumor tissues of all patients. DNA MSI status was analyzed by polymerase chain reaction in 182 samples randomly selected from the 795 cases. Among all CRC tumor tissues, 97 cases (12.2%) were with an MMR protein-deficient (MMR-D) phenotype, whereas 698 cases (87.8%) were with an MMR proteins intact (MMR-I) phenotype. A total of 21 (11.5%) CRCs were identified as having high microsatellite instability, 156 (85.7%) tumors were having microsatellite stability (MSS), and five (2.7%) were having low microsatellite instability. Importantly, MMR status was demonstrated to be moderately consistent with MSI status (κ=0.845, 95% confidence interval [CI] 0.721, 0.969). Unconditional logistic regression analysis revealed age, number of lymph node, tumor diameter, and tumor site as predictors for MSI with a substantial ability to discriminate different MSI status by area under curve of 80.62% using receiver operation curve. Compared with MMR-I, MMR-D was an independent prognostic factor for longer overall survival (hazard ratio =0.340, 95% CI 0.126, 0.919; P=0.034). MMR-D is an independent prognostic factor for better outcome. Our results may provide evidence for individualized diagnosis and treatment of CRC, but this will require further validation in larger sample studies.
ABSTRACT
Kristen rat sarcoma viral oncogene homolog (KRAS) and microsatellite instability (MSI) are prognostic markers of colorectal cancer (CRC). However, the clinical value is still not fully understood, when giving the consideration to both the molecular makers. Five hundred fifty-one patients with CRC were retrospectively assessed by determining their clinicopathological features. KRAS mutations were detected by polymerase chain reaction. MSI, a defect in the mismatch repair (MMR) system, was detected by immunohistochemistry. The prognostic value of KRAS in combination with MSI was studied. Among 551 CRC patients, mutations in KRAS codon 12 and KRAS codon 13 were detected in 34.5% and 10.5% of patients, respectively. Four hundred one tumors were randomly selected to detect for MMR proteins expression. In this analysis, 30 (7.5%) tumors that had at least 1 MMR protein loss were defined as MMR protein-deficient (MMR-D), and the remaining tumors were classed as MMR protein-intact (MMR-I). According to KRAS mutation and MSI status, CRC was classified into 4 groups: Group 1, KRAS-mutated and MMR-I; Group 2, KRAS-mutated and MMR-D; Group 3, KRAS wild and MMR-I; and Group 4, KRAS wild and MMR-D. We found that patients in Group4 had the best prognosis. In conclusion, combination status of KRAS and MSI status may be used as a prognostic biomarker for CRC patient, if validated by larger studies.
Subject(s)
Colorectal Neoplasms/genetics , Microsatellite Instability , Proto-Oncogene Proteins p21(ras)/genetics , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/mortality , Disease-Free Survival , Female , Genetic Markers/genetics , Humans , Male , Middle Aged , Mutation/genetics , Prognosis , Retrospective Studies , Survival Analysis , Young AdultABSTRACT
Gallbladder carcinoma (GBC) is a rare and highly aggressive disease. The diagnosis of this cancer is difficult due to its occult onset. Hence, GBC is often detected late and at an advanced stage. Although physicians and researchers are continually working to improve the treatment for advanced-stage disease, GBC is usually associated with short survival times. The present study describes a case of GBC that was first diagnosed with accompanying cholecystolithiasis at the time of cholecystectomy. Cancer relapse occurred 1.5 years after the cholecystectomy. Multidisciplinary collaboration was involved in the decision-making process for the treatment of this aggressive recurrence, and the survival time was successfully extended to 26 months. Importantly, high-grade intraepithelial neoplasia and positive margins had previously been detected post-cholecystectomy at a different institution, but were ignored. Relapse may have been preventable had the cancer been diagnosed when it was initially observed. Taken together, these findings suggest that multidisciplinary collaboration should be considered for the management of advanced GBC, whereby patients will benefit from improved survival times. Furthermore, it is recommended that samples obtained from patients undergoing cholecystectomy should more carefully analyzed for evidence of cancerous or precancerous tissues.
ABSTRACT
Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase II-III studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition, proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.
Subject(s)
Chemotherapy, Cancer, Regional Perfusion/methods , Peritoneal Neoplasms/secondary , Stomach Neoplasms/pathology , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic , Humans , Hyperthermia, Induced , Neoplasm Recurrence, Local , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/mortality , Prognosis , Stomach Neoplasms/diagnosis , Stomach Neoplasms/drug therapy , Stomach Neoplasms/mortality , Treatment OutcomeABSTRACT
Metastatic temporal bone tumors are rare, and tend to be asymptomatic. The clinical symptoms consist of aural discharge, bleeding, hearing loss and facial nerve paresis. The most common origin of the metastasis is breast cancer, and other sites of the primary tumor include the thyroid gland, brain, lungs, prostate and blood. Clinical reports of hearing loss due to gastric cancer metastatic to temporal bone are rare. In the present study, a case of gastric cancer metastasis to temporal bone without other organ involvement is described. The patient presented with the symptom of hearing loss, and the metastatic tumor was diagnosed by radiological imaging, including magnetic resonance imaging, computed tomography and bone scan.
ABSTRACT
The objective of this study is to develop a new-type biodegradable, biocompatible curcumin-loaded nanoerythrosomes (Cur-RBC-NPs) by means of the sonication method. The size of Cur-RBC-NPs was optimized by varying drug loading parameters. The morphology, size distribution, stability, in vitro release pattern, cellular uptake of nanoparticles and in vitro anti-tumor effects were evaluated, respectively. The results showed the prepared Cur-RBC-NPs were nearly uniform spheres, with an average diameter of (245.7 ± 1.3) nm. Encapsulation efficiency (EE) and load efficiency (LE) of Cur-RBC-NPs were 50.65% ± 1.36% and 6.27% ± 0.29%. And the nanoparticles had a good sustained release property. According to the in vitro experiment, Cur-RBC-NPs were effectively taken in by tumor cells, and exhibited a significant anti-tumor effect. In conclusion, the method for preparing Cur-RBC-NPs is convenient, with a good sustained release behavior and anti-tumor efficacy, and so expected to be a new-type nano-drug delivery system in clinical practice.
Subject(s)
Antineoplastic Agents/pharmacology , Curcumin , Drug Carriers , Nanoparticles , Cell Line, Tumor , Humans , Neoplasms/drug therapy , Particle SizeABSTRACT
Aberrant methylation of the transcription factor AP-2 epsilon (TFAP2E) has been attributed to 5-fluorouridine (5-FU) sensitivity. 5-Aza-2'-deoxycytidine (DAC), an epigenetic drug that inhibits DNA methylation, is able to cause reactive expression of TFAP2E by demethylating activity. This property might be useful in enhancing the sensitivity of cancer cells to 5-FU. However, the effect of DAC is transient because of its instability. Here, we report the use of intelligent gelatinases-stimuli nanoparticles (NPs) to coencapsulate and deliver DAC and 5-FU to gastric cancer (GC) cells. The results showed that NPs encapsulating DAC, 5-FU, or both could be effectively internalized by GC cells. Furthermore, we found that the NPs enhanced the stability of DAC, resulting in improved re-expression of TFAP2E. Thus, the incorporation of DAC into NPs significantly enhanced the sensitivity of GC cells to 5-FU by inhibiting cell growth rate and inducing cell apoptosis. In conclusion, the results of this study clearly demonstrated that the gelatinases-stimuli NPs are an efficient means to simultaneously deliver epigenetic and chemotherapeutic drugs that may effectively inhibit cancer cell proliferation.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Nanoparticles , Stomach Neoplasms/enzymology , Apoptosis/drug effects , Azacitidine/analogs & derivatives , Azacitidine/chemistry , Azacitidine/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Chemistry, Pharmaceutical , DNA Methylation/drug effects , Decitabine , Dose-Response Relationship, Drug , Drug Stability , Enzyme Activation , Epigenesis, Genetic/drug effects , Fluorouracil/chemistry , Fluorouracil/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Time Factors , Transcription Factor AP-2/genetics , Transcription Factor AP-2/metabolismABSTRACT
AIM OF THE STUDY: The prognostic value of the detection of circulating tumour cells (CTCs) in gastric cancer has been studied intensely in recent years. However, the application of different technologies led to inconsistent results between the studies. Here, we performed a meta-analysis of published studies to summarise the evidence. MATERIAL AND METHODS: Medline and ISI Web of Knowledge were searched up to March 2013 using "circulating tumor cells" and "gastric cancer" as search terms. Hazard ratio (HR) with 95% confidence intervals (CIs) for prognostic outcomes and clinical characteristics were extracted from each study. Pooled hazard ratios (HR) and odds ratios (OR) were calculated using random or fixed-effects models. RESULTS: Twelve studies enrolling 774 patients were included. The combined HR estimate for overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were 1.41 (95% CI: 1.28-1.62), 2.99 (95% CI: 2.01-4.45) and 1.64 (95% CI: 1.02-2.62), respectively. Subgroup analysis concerning detection methods and sampling time showed that results of RT-PCR for the OS group and RT-PCR for the DFS group suggest a prognostic significance of CTC detection (pooled HR [95% CI]: 1.45 [1.28-1.65], I(2) = 38%, p = 0.13; 2.99 [2.01-4.45], I(2) = 0%, p = 0.32). In addition, results of the baseline CTC detection group also indicated a significant prognostic value to predict OS and DFS (pooled HR [95% CI]: 1.47 [1.19-1.82], I(2) = 38%, p = 0.14; 2.99 [2.01-4.45], I(2) = 0%, p = 0.32). We simultaneously found that the detection of CTCs correlated with pathological stage (pooled OR [95% CI]: 2.95 [1.65-5.28], I(2) = 56%, p = 0.03), lymph node status (pooled OR [95% CI]: 2.26 [1.50-3.41], I(2) = 37%, p = 0.09), the depth of invasion (pooled OR [95% CI]: 3.21 [1.38-7.43], I(2) = 72%, p = 0.002), and distant metastasis (pooled OR [95% CI]: 2.68 [1.25-5.73], I(2) = 43%, p = 0.15). CONCLUSIONS: Detection of CTCs is associated with poorer prognosis in gastric cancer patients.
ABSTRACT
The occurrence of cervical cancer during pregnancy is extremely rare, particularly small cell carcinoma. Small cell cervical carcinoma (SCCC) is a neuroendocrine tumor with a poor prognosis. This study presents the case of an 18-year-old female with stage IB2 SCCC complicated by pregnancy, who was treated with chemotherapy and radiotherapy. The patient was diagnosed shortly after giving birth, and is the youngest female case to be reported in the world. The patient was treated with cisplatin and etoposide chemotherapy and radiotherapy. Complete remission was achieved following neoadjuvant chemotherapy and radiotherapy, and the patient remains in clinical remission eight months following treatment. Cytological screening, colposcopy and if necessary, biopsy, and selective conization at 14-20 weeks should be considered in the patient evaluation.
ABSTRACT
OBJECTIVE: To generate two genetically engineered mouse models of ErbB2/Neu positive-PTEN deficient breast cancer and to compare their biological properties. METHODS: The genetically engineered mice previously developed with mouse mammary tumor virus (MMTV) promoter driven expression of activated ErbB2/Neu and recombinant Cre (FVB/N-MMTV-NIC) were interbred with Flox-PTEN mice; and FVB/N-ErbB2KI mice, harboring endogenous promoter driven activated ErbB2/Neu expression, FVB/N-MMTV-Cre mice and the flox-PTEN mice were interbred. Neu, Cre and PTEN genes were amplified by PCR for genotyping of the offsprings. ErbB2/Neu and PTEN expression in mammary tumors were detected by immunohistochemistry. Tumor formation time, tumor number, histopathology and lung metastasis were compared between two models, Ki-67 expression was detected by immunohistochemistry, and TUNEL staining of tumor tissues was performed. RESULTS: Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer were generated. The models were confirmed by genotyping and immunohistochemistry. One model with exogenous MMTV promoter driven expression of activated ErbB2/Neu and Cre coupling PTEN disruption was designated as NIC/PTEN(-/-) mice, and the other with MMTV-Cre induced endogenous promoter driven expression of activated ErbB2/Neu with PTEN disruption was designated as ErbB2KI/PTEN(-/-) mice. The tumor formation time in NIC/PTEN(-/-) mice was significantly shorter than that of ErbB2KI/PTEN(-/-) mice (30 vs 368 d, P<0.01); the number of tumor and incidence of lung metastasis was also significantly higher in NIC/PTEN(-/-) mice (10 vs 1-2 and 75.0% vs 37.5%, respectively, Ps<0.01). The Two models displayed distinct histopathological morphology. NIC/PTEN(-/-) tumor showed more Ki-67 positive cells than ErbB2KI/PTEN(-/-) tumor did (86.9%±2.8% vs 37.4%±7.2%, P<0.01), while the amount of cell apoptosis in tumors was not significantly different between two models. CONCLUSION: Two genetically engineered mouse models of ErbB2/Neu positive-PTEN homozygous deficient breast cancer with different phenotypes have been successfully generated, which may provide useful resource for further investigation of the initiation and progression of HER2/ErbB2 breast cancer, as well as for the development of novel prevention and treatment regimens of this malignance.
Subject(s)
Breast Neoplasms/genetics , Disease Models, Animal , Mammary Neoplasms, Animal , PTEN Phosphohydrolase/genetics , Receptor, ErbB-2/genetics , Animals , Female , Gene Deletion , Mammary Tumor Virus, Mouse/genetics , Mice , Mice, TransgenicABSTRACT
Anti-epidermal growth-factor receptor (EGFR) monoclonal antibody (MoAb) treatment for chemotherapy refractory or metastatic colorectal cancer has obtained great achievement. However, not every colorectal patient responds to such molecular-targeted agent well. Biomarkers associated with anti-EGFR resistance are not limited to KRAS mutation up to now. It was recently reported that cross-talking molecular effectors interacted with EGFR-related pathway were also negative predictor for anti-EGFR treatment. However, the limited data, controversial results, and contradictories between in vitro and clinical studies restrict the clinical application of these new biomarkers. Although the current theory of tumor microenvironment supported the application of multi-target treatment, the results from the clinical studies were less than expected. Moreover, WHO or RECIST guideline for response assessment in anti-EGFR MoAb treatment was also queried by recent AIO KRK-0306 trial. This review focuses on these controversies, contradictories, and limitations, in order to uncover the unmet needs in current status of anti-EGFR MoAb treatment in colorectal cancer.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , ErbB Receptors/antagonists & inhibitors , Molecular Targeted Therapy , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cetuximab , Colorectal Neoplasms/metabolism , Drug Resistance, Neoplasm , ErbB Receptors/metabolism , Humans , Molecular Targeted Therapy/adverse effects , Neoplasm Metastasis , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/metabolism , Panitumumab , Practice Guidelines as Topic , Tumor Microenvironment/drug effectsABSTRACT
Radiotherapy is the main locoregional control modality for many types of unresectable tumors, including gastric cancer. However, many patients fail radiotherapy due to intrinsic radioresistance of cancer cells, which has been found to be strongly associated with cancer stem cell (CSC)-like properties. In this study, we developed a nanoparticle formulation to deliver miR-200c, which is reported to inhibit CSC-like properties, and then evaluated its potential activity as a radiosensitizer. miR-200c nanoparticles significantly augmented radiosensitivity in three gastric cancer cell lines (sensitization enhancement ratio 1.13-1.25), but only slightly in GES-1 cells (1.06). In addition to radioenhancement, miR-200c nanoparticles reduced the expression of CD44, a putative CSC marker, and the percentage of CD44(+) BGC823 cells. Meanwhile, other CSC-like properties, including invasiveness and resistance to apoptosis, could be suppressed by miR-200c nanoparticles. CSC-associated radioresistance mechanisms, involving reactive oxygen species levels and DNA repair capacity, were also attenuated. We have demonstrated that miR-200c nanoparticles are an effective radiosensitizer in gastric cancer cells and induce little radiosensitization in normal cells, which suggests that they are as a promising candidate for further preclinical and clinical evaluation.