P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) family of transporters, plays a crucial role in the development of multi-drug resistance (MDR) in cancer treatment. P-gp actively pumps chemotherapeuti...P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) family of transporters, plays a crucial role in the development of multi-drug resistance (MDR) in cancer treatment. P-gp actively pumps chemotherapeutic drugs out of cancer cells, reducing their intracellular concentrations and thereby diminishing their efficacy. This review explores the mechanisms by which P-gp contributes to MDR, including intrinsic and acquired resistance. It also discusses various strategies to inhibit P-gp, such as blocking drug binding sites, interfering with ATP hydrolysis, and altering cell membrane integrity. The potential of fourth-generation P-gp inhibitors and other novel approaches to enhance the effectiveness of cancer therapies is also examined. Understanding and overcoming P-gp-mediated MDR is essential for improving therapeutic outcomes in cancer patients.展开更多
GSPT2 (G1 to S phase transition protein 2) has emerged as a critical regulator of the cell cycle and has garnered increased attention for its role in tumor biology in recent years. This review explores the multifacete...GSPT2 (G1 to S phase transition protein 2) has emerged as a critical regulator of the cell cycle and has garnered increased attention for its role in tumor biology in recent years. This review explores the multifaceted functions of GSPT2, highlighting its involvement in cell cycle regulation and signaling pathways, as well as its potential as a tumor biomarker. By analyzing the latest research findings, we examine the expression patterns of GSPT2 across various tumor types and its correlation with clinical outcomes, underscoring its significance in tumor initiation and progression. Furthermore, we discuss the prospects of GSPT2 as a therapeutic target, providing new insights for future research directions.展开更多
The Cold-Inducible RNA-Binding Protein (CIRBP) family plays a pivotal role in cellular stress responses and tumorigenesis. Recent studies have increasingly highlighted the expression alterations of CIRBP family member...The Cold-Inducible RNA-Binding Protein (CIRBP) family plays a pivotal role in cellular stress responses and tumorigenesis. Recent studies have increasingly highlighted the expression alterations of CIRBP family members across various cancer types and their potential molecular mechanisms. This review provides a comprehensive overview of the structural characteristics and functions of the CIRBP family, alongside their expression profiles in tumors and the regulatory molecular mechanisms involved. By synthesizing current knowledge, this review aims to offer new insights and directions for future cancer therapies, emphasizing the importance of CIRBP proteins in oncological research.展开更多
Background: Pancreatic cancer is one of the most lethal malignancies, with postoperative recurrence severely affecting patient survival and prognosis. This study aims to develop and validate a clinical prediction mode...Background: Pancreatic cancer is one of the most lethal malignancies, with postoperative recurrence severely affecting patient survival and prognosis. This study aims to develop and validate a clinical prediction model for postoperative recurrence in pancreatic cancer patients, incorporating multiple preoperative, intraoperative, and postoperative factors to assist clinical decision-making. Methods: A retrospective study was conducted on 216 patients who underwent surgical treatment for pancreatic malignancy at the First Affiliated Hospital of Chongqing Medical University between January 2015 and January 2023. An independent external validation cohort of 76 patients from the Second Affiliated Hospital of Chongqing Medical University was used to validate the model. Seven independent risk factors for postoperative recurrence were identified through univariate and multivariate Cox regression analyses. The model’s performance was evaluated using the concordance index (C-index) and ROC curves, and its accuracy and clinical value were assessed using calibration curves and decision curve analysis (DCA). Results: The predictive model demonstrated good discriminatory power, with a C-index of 0.72 in the training cohort and 0.66 in the validation cohort. The ROC curves for predicting recurrence at 3, 6, and 12 months postoperatively showed AUC values ranging from 0.72 to 0.83, indicating strong predictive value. Calibration curves and DCA confirmed the model’s accuracy and clinical utility. Conclusion: This study successfully developed and validated a clinical prediction model that incorporates seven independent risk factors for postoperative recurrence in pancreatic cancer. The model provides a useful tool for predicting recurrence risk, aiding in the identification of high-risk patients, and informing clinical decision-making.展开更多
Purpose: Gastrointestinal stromal tumor (GIST) has been considered radiation-resistant and data on the radiotherapy for GIST in previous studies are lacking. The purpose of this article is to accumulate more experienc...Purpose: Gastrointestinal stromal tumor (GIST) has been considered radiation-resistant and data on the radiotherapy for GIST in previous studies are lacking. The purpose of this article is to accumulate more experience in the application of radiotherapy for GISTs. Materials and methods: Review our own case material and the relevant English literature. Results: A huge pelvic GIST after resistance to tyrosine kinase inhibitors (TKIs) has been well controlled by simultaneous-integrated boost intensity-modulated radiation therapy (SIB-IMRT). The time from the initial shrinkage of the mass and subsequent stabilization to now was more than 18 months. The patient was palliated from the series of symptoms caused by tumor compression and well tolerated to the adverse reactions by radiotherapy. And the previous studies have shown that GISTs had a certain sensitivity to radiotherapy. Conclusion: SIB-IMRT may provide a new means of achieving objective response and prolonging survival in selected GIST patients.展开更多
Radiation-induced sarcomas (RIS) are rare but severe long-term complications of radiotherapy (RT). They typically arise years after exposure to ionizing radiation used to treat primary malignancies and complicate pati...Radiation-induced sarcomas (RIS) are rare but severe long-term complications of radiotherapy (RT). They typically arise years after exposure to ionizing radiation used to treat primary malignancies and complicate patient outcomes. Determining the risk associated with these radiation-induced cancers is challenging due to confounding factors such as lifestyle and genetic predisposition. Liposarcomas, which are the most common type of soft tissue sarcomas, originate from adipose tissue and can develop as a late complication of RT. Although they account for a significant portion of soft tissue sarcomas, radiation-induced liposarcomas are still considered rare, making them a noteworthy diagnostic and therapeutic concern. In this report, we present a rare case of radiation-induced dedifferentiated liposarcoma arising 12 years after RT for vulvar cancer. The patient presented with a mass in the groin, which was initially suspected to be a local recurrence. Imaging studies revealed a suspicious lesion on PET/CT, while MRI showed no significant findings. Histopathological evaluation confirmed the diagnosis of dedifferentiated liposarcoma. Surgical resection was performed with a focus on achieving negative margins. A literature review identified nine similar cases, with five being pleomorphic liposarcomas. The average time to presentation was 15 years (interval 3 - 47 years), with a mean radiation dose of 62 Gy. This case highlights the importance of long-term follow-up for cancer survivors and the need for vigilance in diagnosing secondary malignancies following RT.展开更多
Background: Conventional radiation therapy is a technique that uses ionizing radiation to destroy tumor cells. Along with surgery, chemotherapy, hormonotherapy and target therapy, it plays a crucial role in the manage...Background: Conventional radiation therapy is a technique that uses ionizing radiation to destroy tumor cells. Along with surgery, chemotherapy, hormonotherapy and target therapy, it plays a crucial role in the management of breast cancer by reducing its overall mortality and recurrences. Methods: We conducted a retrospective and descriptive study by using the records of patients treated in the radiotherapy department of the Douala General Hospital from January 2015 to December 2019. Data concerning radiation-induced toxicities were collected using a pre-established and pre-tested survey and transferred to the CTCAE Version 4.0 software. Data analysis was performed using SPSS version 20.0. Results: A total of 206 records were selected. The average age was 46.7 ± 8.2 years. The most represented histological type was invasive ductal carcinoma (n = 187, 90.7%). Multimodality treatment was used in every patient in our series with chemotherapy, surgery, and adjuvant radiation therapy (n = 88, 42.7%) been the most represented. More than half of the participants (n = 108, 52.4%) received a total dose >50 grays, only 89 (43.2%) received the classical fractionation of 2 grays/cession, and the average duration of radiation therapy was 36.8 ± 15.4 days. We encountered 155 (75.2%) side effects. There were more acute toxicities than late toxicities, at 115 (74.1%) versus 40 (25.8%). The main acute lesions were radiodermatitis (68.6%), breast pain (16.5%), radiation pneumonitis (12.2%), and acute pericarditis (2.6%). As late lesions, we identified radiodermatitis (52.5%), radiation pneumonitis (32.5%), and lymphoedema (15%). A total dose >50 grays [p 0.001, OR: 2.7 (1.58 - 4.9)], and conservative surgery [p = 0.04, OR: 2.3 (1.3 - 4.1)], seemed to increase the occurrence of early side effects on bivariate analysis. However, after multivariate logistic regression, only a total dose >50 grays [p = 0.005, OR: 2.1 (1.1 - 6.7)] remained a predictive factor associated to early side effects. We found no factors related to late side effect occurrences. Conclusion: The frequency of side effects of radiation therapy for breast cancer at the Douala General Hospital remains relatively high. Both early and late lesions remained present with early toxicities been the most common. Meticulous strategies along with an enhancement of both human and materials resources are paramount in order to reduce their frequency and morbidity.展开更多
Colorectal cancer remains the third most common malignancy worldwide. According to the principles of Traditional Chinese Medicine (TCM), colorectal cancer is related to spleen-deficiency, damp-heat, and toxicity accum...Colorectal cancer remains the third most common malignancy worldwide. According to the principles of Traditional Chinese Medicine (TCM), colorectal cancer is related to spleen-deficiency, damp-heat, and toxicity accumulation. Traditional Chinese medicine has been confirmed to effectively reduce toxic side effects and enhance curative effects of chemotherapy, palliate clinical syndrome, prevent recurrence and metastasis, improve quality of life and immune function, and prolong survival time in colorectal cancer. However, TCM theoretical and syndrome differentiation study has lagged far behind due to progression of therapy model in colorectal cancer. As a type of drug treatment, there are some common biological basis between chemotherapy, targeted therapy and anti-cancer herb therapy in colorectal cancer, such as apoptosis, cell senescence and autophagy. There are growing needs to explore the effect mechanism and compatibility of anti-cancer herbs, to further enhance the efficacy of TCM treatment in colorectal cancer.展开更多
Primary malignant brain tumors are a leading cause of cancer-related death in children. This Phase II study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in children who developed progressio...Primary malignant brain tumors are a leading cause of cancer-related death in children. This Phase II study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in children who developed progression during standard treatment. A total of 43 children were recruited to the study, but only 41 met eligibility criteria. There were twelve cases of glioblastoma multiforme (GBM), eight anaplastic astrocytomas (AA), twelve diffuse intrinsic pontine gliomas (DIPG), three supertentorial primitive neuroectodermal tumors (sPNET), three cases of medulloblastoma and one case each of anaplastic ependymoma (AE), atypical teratoid rhabdoid tumor (AT/RT), and disseminated pilocytic astrocytoma (PAD). ANP was administered intravenously daily every four hours (median dose of A10 8.74 g/kg/d and AS2-1 0.35 g/kg/d), until objective response (OR) was documented, and then a further eight months. All enrolled patients were included in safety, but only eligible patients in the efficacy evaluation. A total of 12.2% of patients obtained OR;2.4% complete response (CR) and 9.8% partial response (PR). Stable disease (SD) was determined in 17.1% and progressive disease (PD) in 43.9% of cases. There were 26.8% of nonevaluable (NE) cases due to premature discontinuation. Out of five OR cases, four patients were diagnosed with recurrent DIPG and one with recurrent AA. Median progression-free survival (PFS) was 2.5 months. Median overall survival was 4.8 months. OS at 6 months was 46.3%, one year was 12.2%, and 4.8% at two, five, and ten years. The longest survivor is a patient diagnosed with DIPG and gliosarcoma who remains alive more than 15 years. A group of eleven patients reported grade 3 and 4 toxicity including hypernatremia in eight cases, somnolence in two cases, and hypokalemia in one case. There were no chronic toxicities, and the quality of life was very good. The largest group of patients were represented by DIPG, GBM, and AA. The best results were obtained in the DIPG and AA groups. In the DIPG group, CR was in 8.3%, PR was 25%, median PFS was 4.8 months, median OS was 6.1 months, and OS at 6 months was 58.3%, at one year 25%, and 8.3% at two, five, and ten years. In the AA group, PR was 12.5%, median PFS was 3.7 months, median OS was 4.7 months, and OS at 6 months was 37.5%, and 12.5%, at one, two, five, and ten years. In conclusion, antineoplastons showed efficacy and acceptable toxicity in patients with recurrent, refractory or progressive primary brain tumors.展开更多
Peritoneal metastasis of gastric cancer is mainly caused by the dispersion of free cancer cells from the serosal surface of the invaded stomach, from surgically transected lymphatic channels, and from tumor cell-conta...Peritoneal metastasis of gastric cancer is mainly caused by the dispersion of free cancer cells from the serosal surface of the invaded stomach, from surgically transected lymphatic channels, and from tumor cell-containing blood from the primary lesion into the peritoneal cavity. Intraperitoneal chemotherapy (IPC) combined with surgery has performed for the prevention and treatment of peritoneal metastasis in gastric cancer. The efficacy of this technique is influenced by the pharmacokinetic advantage achievable with the anticancer drug, timing of administration, combination with hyperthermia, and tumor volume. The pharmacokinetic advantage for peritoneal cavity exposure relative to peripheral circulation by intraperitoneal delivery for drugs including cisplatin (10-fold advantage), mitomycin C (20- to 30-fold advantage), docetaxel (500-fold advantage), and paclitaxel (1000-fold advantage) has been confirmed. To avoid uneven drug distribution in the peritoneal cavity and the re-growth of residual tumor, it seems to be reasonable to perform IPC perioperatively;however, early perioperative intraperitoneal chemotherapy (EPIC) has a relatively high morbidity rate compared with intraoperative IPC. Hyperthermia has both cytotoxicity of itself and a synergistic effect with anticancer drugs, especially mitomycin C. In the adjuvant setting, patients with either hyperthermic intraperitoneal chemotherapy (HIPEC) or EPIC showed a significant improvement of survival compared to those with surgery alone. In addition, extensive intraoperative peritoneal lavage (EIPL) seems also to be a reasonable method to reduce free cancer cells in the peritoneal cavity. For the treatment of peritoneal metastasis, cytoreductive surgery which achieves R0 or R1 resection followed by IPC has demonstrated a survival benefit, whereas gross residual tumor (R2) treated by IPC has shown poor prognosis. Extensive cytoreductive surgery, such as peritonectomy, followed by IPC achieved long-term survival for selected patients, though this aggressive procedure led to high morbidity and mortality rates. It seems that combined chemotherapy (systemically and intraperitoneally) followed by conversion surgery can be expected to be a powerful procedure for the patients with gross peritoneal tumors.展开更多
Treatment of recurrent glioblastoma multiforme (RGBM) creates one of the most difficult challenges to neuro-oncology. The purpose of this study is to evaluate the outcome of adults with high-grade glioma with special ...Treatment of recurrent glioblastoma multiforme (RGBM) creates one of the most difficult challenges to neuro-oncology. The purpose of this study is to evaluate the outcome of adults with high-grade glioma with special attention to RGBM patients treated with Antineoplastons (ANP) A10 and AS2-1 injections. The study was conducted according to Protocol BT-21, which accrued patients who failed standard radiation therapy (RT) and chemotherapy. There were 40 candidates registered in the study. Among the intent-to-treat (ITT) population, there were 30 cases of RGBM that progressed during and after prior treatment, 4 patients with anaplastic astrocytoma (AA), 1 with anaplastic mixed glioma (AMG), and 5 with persistent GBM. The aim of this paper is to evaluate the responses, survival and toxicity of all 40 patients, the efficacy in 30 patients with RGBM, and in 24 patients with RGBM who received at least 28 days of ANP (ERGBM). All RGBM patients were treated before with RT and chemotherapy, except one patient who only had surgery (patient refused radiation). In this group, 63% had one recurrence, 30% had two recurrences, and 7% had three recurrences. The median duration of ANP and ITT was 12 weeks and the median dosage of ANP A10 was 6.52 g/kg/d and ANP AS2-1 was 0.23 g/kg/d. Responses were assessed by gadolinium-enhanced magnetic resonance imaging (MRI) repeated every eight weeks. In the ITT population, objective responses (ORs) were determined in 10% of cases (complete response—CR, and partial response—PR in 5% each). Progression-free survival (PFS) in ITT at six months was 17.5%. Overall survival (OS) was 28.3% at one year, 2.6% at two years, five and ten years. In the RGBM population, objective responses (ORs) were determined in 13.3% of cases (CR and PR in 6.7% each). PFS in RGBM at six months was 16.7%. OS was 34.7% at one year, 3.47% at two years, five?and ten years. In the ERGBM population, ORs were determined in 16.7% of cases (CR and PR in?8.3% each). PFS in ERGBM at six months was 20.8%, OS was 39.3% at one year, 4.4% at two years, five and ten years. The treatment was well-tolerated with reversible Grades 3 and 4 toxicity in 17.5% of patients (7 patients who experienced multiple toxicities) and no chronic toxicity. In conclusion, the study reached efficacy endpoint. ANP is well-tolerated and compares favorably to the current treatment for RGBM.展开更多
Purpose: The main objective of the study was to evaluate the effect of air gaps of 0 - 5.0 cm between bolus and skin for 1.0 cm Superflab bolus on surface dose (DSurf) and depth of maximum dose (dmax) in solid water a...Purpose: The main objective of the study was to evaluate the effect of air gaps of 0 - 5.0 cm between bolus and skin for 1.0 cm Superflab bolus on surface dose (DSurf) and depth of maximum dose (dmax) in solid water and Rando? phantoms. Methods: In this work, the effects of bolus to surface distance on DSurf and variation in dmax were analyzed in a solid water phantom and in an anthropomorphic Rando? phantom for different field sizes, using Gafchromic? EBT films and farmer chamber. Results: For field sizes of 5 × 5 cm2 the DSurf is significantly affected by increasing air gaps greater than 5 mm. For field sizes larger than 10 × 10 cm2, DSurf is nearly the same for air gaps of 0 - 5.0 cm. For small fields and 6 MV photon beam, dmax increases with increasing air gap, while for 10 MV beam and smaller field sizes (i.e. 5 × 5 and 10 × 10 cm2) the dmax first decreases and then increases with the air gaps. For both 3DCRT and IMRT plans on Rando?, DSurf reduction is more prominent with increasing air gaps. Conclusion: For field sizes larger than 10 × 10 cm2 DSurf is largely unaffected by air gaps. However, smaller air gap results in shallower dmax for both 6 MV and 10 MV photon beams at all fields sizes. Special consideration should be taken to reduce air gaps between bolus and skin for field sizes smaller than 10 × 10 cm2 or when surface contour variations are greater or when the bolus covers small area and at the border of the field.展开更多
Squamous cell carcinoma accounts for 90% of all oral cancers. It may affect any anatomical site in the mouth, but most commonly the tongue and the floor of the mouth. It usually arises from a pre-existing potentially ...Squamous cell carcinoma accounts for 90% of all oral cancers. It may affect any anatomical site in the mouth, but most commonly the tongue and the floor of the mouth. It usually arises from a pre-existing potentially malignant lesion, and occasionally de novo;but in either case from within a field of precancerized epithelium. The use of tobacco and betel quid, heavy drinking of alcoholic beverages and a diet low in fresh fruits and vegetables are well known risk factors for oral squamous cell carcinoma. Important risk factors related to the carcinoma itself that are associated with a poor prognosis include large size of the tumour at the time of diagnosis, the presence of metastases in regional lymphnodes, and a deep invasive front of the tumour. Squamous cell carcinoma is managed by surgery, radiation, and chemotherapy singularly or in combination;but regardless of the treatment modality, the five-year survival rate is poor at about 50%. This can be attributed to the fact that about two-thirds of persons with oral squamous cell carcinoma already have a large lesion at the time of diagnosis.展开更多
Background: Since advanced hepatocellular carcinoma (HCC) is potentially fatal, and patients’ quality of life (QOL) often deteriorates during their treatment, improving the prognosis and QOL of patients given chemoth...Background: Since advanced hepatocellular carcinoma (HCC) is potentially fatal, and patients’ quality of life (QOL) often deteriorates during their treatment, improving the prognosis and QOL of patients given chemotherapy is very important. In addition, cost-effective treatments are highly desirable when chemotherapy must be given repeatedly. The aim of this study was to evaluate the efficacy and usefulness of 5-fluorouracil (5-FU) and high-concentration cisplatin by short-term hepatic arterial infusion chemotherapy (3-day FPL) in advanced HCC patients. Methods: Thirty patients with unresectable advanced HCC were enrolled. The patients underwent hepatic arterial infusion chemotherapy via the implanted port system with 5-FU on days 1 - 3 and a fine-powder formulation of cisplatin in suspended pre-warmed lipiodol on day 2 every 4 to 10 weeks. Tumor response was assessed one month later with CT. Results: All patients had evidence of portal vein invasion (Vp2-4). Four patients achieved a complete response (CR), 8 patients achieved a partial response (PR), and 7 patients had stable disease (SD). The median progression-free survival (PFS) and overall survival (OS) were 198 days and 452 days, respectively. The OS was significantly longer in the successful disease control group (CR, PR, and SD) than in the progressive disease group (P < 0.005). Conclusions: Three-day FPL was effective and tolerable in advanced HCC patients due to its shorter time of administration than conventional FP therapy. Therefore, repetitive 3-day FPL appears useful and contributes to improving the prognosis and QOL of patients with advanced HCC. In addition, this protocol is a cost-effective treatment.展开更多
Cordycepin is an active component of parasitic fungus, Cordyceps militaris, and investigated for its pharmacologic efficacy. Increasing evidence supports the anti-tumoral effects of Cordycepin in various types of huma...Cordycepin is an active component of parasitic fungus, Cordyceps militaris, and investigated for its pharmacologic efficacy. Increasing evidence supports the anti-tumoral effects of Cordycepin in various types of human solid tumors. We sought to determine the effects of Cordycepin on oral squamous cell carcinoma in vitro and in vivo. Two oral squamous cell carcinoma cell lines, KB and HSC3, were used in this study. Cells were treated with Cordycepin or diluent, followed by determinations of proliferation by sulforhodamine method and apoptosis by TUNEL assay in vitro. For in vivo experiments, tumor cells were transplanted into nude mice, followed by treatment with Cordycepin or control diluent. In addition, cells were examined for expression of adenosine receptor isotypes, and tested whether cordycepin-induced effects were mediated through adenosine receptors by combinatorial treatment of cordycepin and antagonists specific to each isotype of adenosine receptors. Two cell lines expressed protein of all types of adenosine receptors stronger than normal oral keratinocytes. Cordycepin showed anti-proliferating effect and apoptotic effect on both cell lines in vitro in a dose dependent manner. However, any adenosine receptors did not reverse the effect of cordycepin. In our in vivo experiments, cordycepin failed to decrease the tumor volume significantly, and failed to induce more apoptosis of tumor cells. Cordycepin has anti-proliferating effect and induces apoptosis not mediated by adenosine receptor on oral squamous cell carcinoma cells in vitro. However, in vivo results suggest that cordycepin in itself has a limited value as a novel chemotherapeutic agent for oral squamous cell carcinoma.展开更多
Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies ar...Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies are needed for patients whose tumor recurs after first-line treatment. This single-arm, two-stage, interventional Phase II study evaluated the efficacy and safety of a combination of antineoplastons A10 and AS2-1. Nineteen patients were enrolled in the study (safety population), but fifteen patients with a median age of 9.4 years who met eligibility criteria were evaluated. The majority of subjects (12/15) were Caucasian and 8/15 (53%) were female. More than half (53%) of patients were diagnosed with glioblastoma and 33% with anaplastic astrocytoma. All patients had failed standard therapy including surgery, radiation, and chemotherapy. Antineoplastons were administered intravenously every four hours (median dose of A10 6.9 g/kg/d and AS2-1 0.30 g/kg/d) until objective response was documented and thereafter for a further 8 months. Clinical evaluations were performed every 8 weeks. All patients enrolled in the study were included in the safety analysis but only patients fulfilling the inclusion criteria were included in the efficacy evaluation. The duration of treatment with antineoplastons ranged from 2 weeks to 120 weeks. A complete response was documented in 2/15 (13%), partial response in 2/15 (13%), stable disease in 3/15 (20%). Progression-free survival at six months was 47% and overall survival (OS) at one year was 33.3%. One patient (6.7%) survived 10 years from treatment start. A small group of patients suffered reversible Grade 3 and 4 toxicities including hypernatremia 2/19 (11%) and decrease of neutrophils 1/19 (5%). There were no chronic toxicities. There was improvement of quality of life in patients who had objective response. It is concluded that antineoplastons show efficacy with an acceptable profile in this cohort of patients with recurrent high-grade glioma.展开更多
The present comparative review discusses conservation of early evolutionary, relic genetics in the genome of man, which determine two different mechanistic reductive division systems expressed by normal, human diploid...The present comparative review discusses conservation of early evolutionary, relic genetics in the genome of man, which determine two different mechanistic reductive division systems expressed by normal, human diploid cells. The divisions were orderly and segregated genomes reductively to near-diploid daughter cells, which showed gain of a proliferative advantage (GPA) over cells of origin. This fact of GPA expression is a fundamental requirement for initiation of tumorigenesis. The division systems were responses to a carcinogen-free induction system, consisting of short (1 - 3 days) exposures of young cells to nutritional deprivation of amino acid glutamine (AAD). In recovery growth (2 - 4 days) endo-tetra/ochtoploid cells and normal diploid metaphase cells demonstrated chromosomal reductive divisions to respectively heterozygous and homozygous altered daughter cells. Both division systems showed co-segregating whole complements, which for reduction of the diploid metaphases could only arise from gonomeric-based autonomous behavior of maternal and paternal (mat/pat) genomes. The timely associated appearance with these latter divisions was fast growing small-cells (1/2 volume-size reduced from normal diploidy), which became homozygous from haploid, genomic doubling. Both reductive divisions thus produced genome altered progeny cells with GPA, which was associated with pre-cancer-like cell-phenotypic changes. Since both “undesirable” reductive divisions expressed orderly division sequences, their genetic controls were assumed to be “old genetics”, evolutionarily conserved in the genome of man. Support for this idea was a search for evidential material in the evolutionary record from primeval time, when haploid organisms were established. The theory was that endopolyploid and gonomery-based reductive divisions relieved the early eukaryotic organisms from accidental, non-proliferative diploidy and polyploidy, bringing the organism back to vegetative haploid proliferation. Asexual cycles were common for maintenance of propagating haploid and diploid early unicellular eukaryotes. Reduction of accidental diploidy was referred to as “one-step meiosis” which meant gonomeric-based maternal and paternal genomic independent segregations. This interpretation was supported by exceptional chromosomal behaviors. However, multiple divisions expressing non-disjunction was the choice-explanation from evolutionists, which today is also suggested for the rarer LL-1 near haploid leukemia. These preserved non-mitotic mechanistic divisions systems are today witnessed in apomixes and parthenogenesis in many animal phyla. Thus, the indications are the modern genome of man harbors, relic-genetics from past “good” evolvements assuring “stable” proliferation of ancient, primitive eukaryotes, but with cancer-like effects for normal human cells.展开更多
Antineoplastons are peptide and amino acid derivatives that occur naturally in the human body. They inhibit the growth of neoplastic cells without growth inhibition of normal cells. Phenylacetylglutaminate (PG) is an ...Antineoplastons are peptide and amino acid derivatives that occur naturally in the human body. They inhibit the growth of neoplastic cells without growth inhibition of normal cells. Phenylacetylglutaminate (PG) is an active ingredient of antineoplastons A10 and AS2-1 (ANP) and is also a metabolic by-product of phenylbutyrate (PB). The formulation of antineoplaston AS2-1 is a 4:1 mixture of phenylacetate (PN) and PG. Antineoplaston A10 is a 4:1 mixture of PG and isoPG. This study investigates the molecular mechanism of action of PG and PN. The Human U87 glioblastoma (GBM) cell line was used as the model system in this study. A total human gene array screen using the Affymetrix Human Genome plus 2.0 oligonucleotide arrays was performed using mRNA derived from U87 cells exposed to PG and PN. Pathway analysis was performed to allow the visualization of effect on metabolic pathways and gene interaction networks. Our preliminary results indicate that PG and PN interrupt signal transduction in RAS/MAPK/ERK and PI3K/AKT/PTEN pathways, interfere with cell cycle, decrease metabolism and promote apoptosis in human U87 GBM cells. The effect on multiple cellular pathways and targets, suggests that ANP and PB are promising candidates for clinical studies in GBM.展开更多
Introduction: Systematic lymphadenectomy and ligation of the feeding artery is extremely important when performing radical resection in colorectal cancer. However, vascular surgery via laparoscopy requires advanced sk...Introduction: Systematic lymphadenectomy and ligation of the feeding artery is extremely important when performing radical resection in colorectal cancer. However, vascular surgery via laparoscopy requires advanced skills and techniques;thus, this procedure needs to be simplified while maintaining quality of the surgery to make it a preferred technique for the surgeons. Methods: There were 49 patients who underwent laparoscopic sigmoidectomy or anterior resection till T2 level for sigmoid colon cancer and recto-sigmoid colon cancer. We analyzed short-term and long-term outcomes between stapling ligation and clipping ligation techniques used in these surgeries. Results: The mean volume of blood loss in the stapling ligation group was 12.8 ± 12.3 ml, which was significantly lower than 41.9 ± 71.2 ml of mean volume of blood loss in the clipping ligation group. There was no significant difference in the mean duration of surgery, the mean number of harvested lymph nodes, morbidity, recurrence, and 5-year relapse free survival rates between the 2 groups. Conclusions: This study demonstrates a surgical technique using staplers for vascular treatment of tumor-feeding arteries as a new technical improvement in laparoscopic colectomy for the treatment of early-stage colon cancer. We found that the described procedure was technically safe, simple, convenient, and oncologically valid.展开更多
Colorectal cancer (CRC) is the second leading cause of cancer death related mortality with 1.2 million new cases diagnosed annually worldwide. Despite remarkable advances in the treatment of resectable CRC, advanced d...Colorectal cancer (CRC) is the second leading cause of cancer death related mortality with 1.2 million new cases diagnosed annually worldwide. Despite remarkable advances in the treatment of resectable CRC, advanced disease that recurs following initial two lines of chemotherapy, remains incurable. Targeted therapies using a single agent or in combination with other drugs have been tested in a number of clinical trials, with only moderate improvement. Here we present preliminary findings of improved overall survival (OS) using a combination of sodium phenylbutyrate with various targeted and chemotherapeutic agents in stage IV CRC patients who had failed at least two lines of chemotherapy. Results suggest a strategy of simultaneous interruption of signal transduction involving EGFR (VEGF)?KRAS-ERK and PI3K-AKT pathways and interference with cell cycle, cancer cell metabolism, maintenance of cancerous stem cells, and promotion of apoptosis. In a group of 15 patients, median OS was higher compared to other third-line therapies (14.7 months compared to between 4.8 and 9.5 months in other studies). Given the understanding that our findings are preliminary, we propose the validation of our initial results using a well-designed phase I/II trial in recurrent advanced colorectal cancer.展开更多
文摘P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) family of transporters, plays a crucial role in the development of multi-drug resistance (MDR) in cancer treatment. P-gp actively pumps chemotherapeutic drugs out of cancer cells, reducing their intracellular concentrations and thereby diminishing their efficacy. This review explores the mechanisms by which P-gp contributes to MDR, including intrinsic and acquired resistance. It also discusses various strategies to inhibit P-gp, such as blocking drug binding sites, interfering with ATP hydrolysis, and altering cell membrane integrity. The potential of fourth-generation P-gp inhibitors and other novel approaches to enhance the effectiveness of cancer therapies is also examined. Understanding and overcoming P-gp-mediated MDR is essential for improving therapeutic outcomes in cancer patients.
文摘GSPT2 (G1 to S phase transition protein 2) has emerged as a critical regulator of the cell cycle and has garnered increased attention for its role in tumor biology in recent years. This review explores the multifaceted functions of GSPT2, highlighting its involvement in cell cycle regulation and signaling pathways, as well as its potential as a tumor biomarker. By analyzing the latest research findings, we examine the expression patterns of GSPT2 across various tumor types and its correlation with clinical outcomes, underscoring its significance in tumor initiation and progression. Furthermore, we discuss the prospects of GSPT2 as a therapeutic target, providing new insights for future research directions.
文摘The Cold-Inducible RNA-Binding Protein (CIRBP) family plays a pivotal role in cellular stress responses and tumorigenesis. Recent studies have increasingly highlighted the expression alterations of CIRBP family members across various cancer types and their potential molecular mechanisms. This review provides a comprehensive overview of the structural characteristics and functions of the CIRBP family, alongside their expression profiles in tumors and the regulatory molecular mechanisms involved. By synthesizing current knowledge, this review aims to offer new insights and directions for future cancer therapies, emphasizing the importance of CIRBP proteins in oncological research.
文摘Background: Pancreatic cancer is one of the most lethal malignancies, with postoperative recurrence severely affecting patient survival and prognosis. This study aims to develop and validate a clinical prediction model for postoperative recurrence in pancreatic cancer patients, incorporating multiple preoperative, intraoperative, and postoperative factors to assist clinical decision-making. Methods: A retrospective study was conducted on 216 patients who underwent surgical treatment for pancreatic malignancy at the First Affiliated Hospital of Chongqing Medical University between January 2015 and January 2023. An independent external validation cohort of 76 patients from the Second Affiliated Hospital of Chongqing Medical University was used to validate the model. Seven independent risk factors for postoperative recurrence were identified through univariate and multivariate Cox regression analyses. The model’s performance was evaluated using the concordance index (C-index) and ROC curves, and its accuracy and clinical value were assessed using calibration curves and decision curve analysis (DCA). Results: The predictive model demonstrated good discriminatory power, with a C-index of 0.72 in the training cohort and 0.66 in the validation cohort. The ROC curves for predicting recurrence at 3, 6, and 12 months postoperatively showed AUC values ranging from 0.72 to 0.83, indicating strong predictive value. Calibration curves and DCA confirmed the model’s accuracy and clinical utility. Conclusion: This study successfully developed and validated a clinical prediction model that incorporates seven independent risk factors for postoperative recurrence in pancreatic cancer. The model provides a useful tool for predicting recurrence risk, aiding in the identification of high-risk patients, and informing clinical decision-making.
文摘Purpose: Gastrointestinal stromal tumor (GIST) has been considered radiation-resistant and data on the radiotherapy for GIST in previous studies are lacking. The purpose of this article is to accumulate more experience in the application of radiotherapy for GISTs. Materials and methods: Review our own case material and the relevant English literature. Results: A huge pelvic GIST after resistance to tyrosine kinase inhibitors (TKIs) has been well controlled by simultaneous-integrated boost intensity-modulated radiation therapy (SIB-IMRT). The time from the initial shrinkage of the mass and subsequent stabilization to now was more than 18 months. The patient was palliated from the series of symptoms caused by tumor compression and well tolerated to the adverse reactions by radiotherapy. And the previous studies have shown that GISTs had a certain sensitivity to radiotherapy. Conclusion: SIB-IMRT may provide a new means of achieving objective response and prolonging survival in selected GIST patients.
文摘Radiation-induced sarcomas (RIS) are rare but severe long-term complications of radiotherapy (RT). They typically arise years after exposure to ionizing radiation used to treat primary malignancies and complicate patient outcomes. Determining the risk associated with these radiation-induced cancers is challenging due to confounding factors such as lifestyle and genetic predisposition. Liposarcomas, which are the most common type of soft tissue sarcomas, originate from adipose tissue and can develop as a late complication of RT. Although they account for a significant portion of soft tissue sarcomas, radiation-induced liposarcomas are still considered rare, making them a noteworthy diagnostic and therapeutic concern. In this report, we present a rare case of radiation-induced dedifferentiated liposarcoma arising 12 years after RT for vulvar cancer. The patient presented with a mass in the groin, which was initially suspected to be a local recurrence. Imaging studies revealed a suspicious lesion on PET/CT, while MRI showed no significant findings. Histopathological evaluation confirmed the diagnosis of dedifferentiated liposarcoma. Surgical resection was performed with a focus on achieving negative margins. A literature review identified nine similar cases, with five being pleomorphic liposarcomas. The average time to presentation was 15 years (interval 3 - 47 years), with a mean radiation dose of 62 Gy. This case highlights the importance of long-term follow-up for cancer survivors and the need for vigilance in diagnosing secondary malignancies following RT.
文摘Background: Conventional radiation therapy is a technique that uses ionizing radiation to destroy tumor cells. Along with surgery, chemotherapy, hormonotherapy and target therapy, it plays a crucial role in the management of breast cancer by reducing its overall mortality and recurrences. Methods: We conducted a retrospective and descriptive study by using the records of patients treated in the radiotherapy department of the Douala General Hospital from January 2015 to December 2019. Data concerning radiation-induced toxicities were collected using a pre-established and pre-tested survey and transferred to the CTCAE Version 4.0 software. Data analysis was performed using SPSS version 20.0. Results: A total of 206 records were selected. The average age was 46.7 ± 8.2 years. The most represented histological type was invasive ductal carcinoma (n = 187, 90.7%). Multimodality treatment was used in every patient in our series with chemotherapy, surgery, and adjuvant radiation therapy (n = 88, 42.7%) been the most represented. More than half of the participants (n = 108, 52.4%) received a total dose >50 grays, only 89 (43.2%) received the classical fractionation of 2 grays/cession, and the average duration of radiation therapy was 36.8 ± 15.4 days. We encountered 155 (75.2%) side effects. There were more acute toxicities than late toxicities, at 115 (74.1%) versus 40 (25.8%). The main acute lesions were radiodermatitis (68.6%), breast pain (16.5%), radiation pneumonitis (12.2%), and acute pericarditis (2.6%). As late lesions, we identified radiodermatitis (52.5%), radiation pneumonitis (32.5%), and lymphoedema (15%). A total dose >50 grays [p 0.001, OR: 2.7 (1.58 - 4.9)], and conservative surgery [p = 0.04, OR: 2.3 (1.3 - 4.1)], seemed to increase the occurrence of early side effects on bivariate analysis. However, after multivariate logistic regression, only a total dose >50 grays [p = 0.005, OR: 2.1 (1.1 - 6.7)] remained a predictive factor associated to early side effects. We found no factors related to late side effect occurrences. Conclusion: The frequency of side effects of radiation therapy for breast cancer at the Douala General Hospital remains relatively high. Both early and late lesions remained present with early toxicities been the most common. Meticulous strategies along with an enhancement of both human and materials resources are paramount in order to reduce their frequency and morbidity.
文摘Colorectal cancer remains the third most common malignancy worldwide. According to the principles of Traditional Chinese Medicine (TCM), colorectal cancer is related to spleen-deficiency, damp-heat, and toxicity accumulation. Traditional Chinese medicine has been confirmed to effectively reduce toxic side effects and enhance curative effects of chemotherapy, palliate clinical syndrome, prevent recurrence and metastasis, improve quality of life and immune function, and prolong survival time in colorectal cancer. However, TCM theoretical and syndrome differentiation study has lagged far behind due to progression of therapy model in colorectal cancer. As a type of drug treatment, there are some common biological basis between chemotherapy, targeted therapy and anti-cancer herb therapy in colorectal cancer, such as apoptosis, cell senescence and autophagy. There are growing needs to explore the effect mechanism and compatibility of anti-cancer herbs, to further enhance the efficacy of TCM treatment in colorectal cancer.
文摘Primary malignant brain tumors are a leading cause of cancer-related death in children. This Phase II study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in children who developed progression during standard treatment. A total of 43 children were recruited to the study, but only 41 met eligibility criteria. There were twelve cases of glioblastoma multiforme (GBM), eight anaplastic astrocytomas (AA), twelve diffuse intrinsic pontine gliomas (DIPG), three supertentorial primitive neuroectodermal tumors (sPNET), three cases of medulloblastoma and one case each of anaplastic ependymoma (AE), atypical teratoid rhabdoid tumor (AT/RT), and disseminated pilocytic astrocytoma (PAD). ANP was administered intravenously daily every four hours (median dose of A10 8.74 g/kg/d and AS2-1 0.35 g/kg/d), until objective response (OR) was documented, and then a further eight months. All enrolled patients were included in safety, but only eligible patients in the efficacy evaluation. A total of 12.2% of patients obtained OR;2.4% complete response (CR) and 9.8% partial response (PR). Stable disease (SD) was determined in 17.1% and progressive disease (PD) in 43.9% of cases. There were 26.8% of nonevaluable (NE) cases due to premature discontinuation. Out of five OR cases, four patients were diagnosed with recurrent DIPG and one with recurrent AA. Median progression-free survival (PFS) was 2.5 months. Median overall survival was 4.8 months. OS at 6 months was 46.3%, one year was 12.2%, and 4.8% at two, five, and ten years. The longest survivor is a patient diagnosed with DIPG and gliosarcoma who remains alive more than 15 years. A group of eleven patients reported grade 3 and 4 toxicity including hypernatremia in eight cases, somnolence in two cases, and hypokalemia in one case. There were no chronic toxicities, and the quality of life was very good. The largest group of patients were represented by DIPG, GBM, and AA. The best results were obtained in the DIPG and AA groups. In the DIPG group, CR was in 8.3%, PR was 25%, median PFS was 4.8 months, median OS was 6.1 months, and OS at 6 months was 58.3%, at one year 25%, and 8.3% at two, five, and ten years. In the AA group, PR was 12.5%, median PFS was 3.7 months, median OS was 4.7 months, and OS at 6 months was 37.5%, and 12.5%, at one, two, five, and ten years. In conclusion, antineoplastons showed efficacy and acceptable toxicity in patients with recurrent, refractory or progressive primary brain tumors.
文摘Peritoneal metastasis of gastric cancer is mainly caused by the dispersion of free cancer cells from the serosal surface of the invaded stomach, from surgically transected lymphatic channels, and from tumor cell-containing blood from the primary lesion into the peritoneal cavity. Intraperitoneal chemotherapy (IPC) combined with surgery has performed for the prevention and treatment of peritoneal metastasis in gastric cancer. The efficacy of this technique is influenced by the pharmacokinetic advantage achievable with the anticancer drug, timing of administration, combination with hyperthermia, and tumor volume. The pharmacokinetic advantage for peritoneal cavity exposure relative to peripheral circulation by intraperitoneal delivery for drugs including cisplatin (10-fold advantage), mitomycin C (20- to 30-fold advantage), docetaxel (500-fold advantage), and paclitaxel (1000-fold advantage) has been confirmed. To avoid uneven drug distribution in the peritoneal cavity and the re-growth of residual tumor, it seems to be reasonable to perform IPC perioperatively;however, early perioperative intraperitoneal chemotherapy (EPIC) has a relatively high morbidity rate compared with intraoperative IPC. Hyperthermia has both cytotoxicity of itself and a synergistic effect with anticancer drugs, especially mitomycin C. In the adjuvant setting, patients with either hyperthermic intraperitoneal chemotherapy (HIPEC) or EPIC showed a significant improvement of survival compared to those with surgery alone. In addition, extensive intraoperative peritoneal lavage (EIPL) seems also to be a reasonable method to reduce free cancer cells in the peritoneal cavity. For the treatment of peritoneal metastasis, cytoreductive surgery which achieves R0 or R1 resection followed by IPC has demonstrated a survival benefit, whereas gross residual tumor (R2) treated by IPC has shown poor prognosis. Extensive cytoreductive surgery, such as peritonectomy, followed by IPC achieved long-term survival for selected patients, though this aggressive procedure led to high morbidity and mortality rates. It seems that combined chemotherapy (systemically and intraperitoneally) followed by conversion surgery can be expected to be a powerful procedure for the patients with gross peritoneal tumors.
文摘Treatment of recurrent glioblastoma multiforme (RGBM) creates one of the most difficult challenges to neuro-oncology. The purpose of this study is to evaluate the outcome of adults with high-grade glioma with special attention to RGBM patients treated with Antineoplastons (ANP) A10 and AS2-1 injections. The study was conducted according to Protocol BT-21, which accrued patients who failed standard radiation therapy (RT) and chemotherapy. There were 40 candidates registered in the study. Among the intent-to-treat (ITT) population, there were 30 cases of RGBM that progressed during and after prior treatment, 4 patients with anaplastic astrocytoma (AA), 1 with anaplastic mixed glioma (AMG), and 5 with persistent GBM. The aim of this paper is to evaluate the responses, survival and toxicity of all 40 patients, the efficacy in 30 patients with RGBM, and in 24 patients with RGBM who received at least 28 days of ANP (ERGBM). All RGBM patients were treated before with RT and chemotherapy, except one patient who only had surgery (patient refused radiation). In this group, 63% had one recurrence, 30% had two recurrences, and 7% had three recurrences. The median duration of ANP and ITT was 12 weeks and the median dosage of ANP A10 was 6.52 g/kg/d and ANP AS2-1 was 0.23 g/kg/d. Responses were assessed by gadolinium-enhanced magnetic resonance imaging (MRI) repeated every eight weeks. In the ITT population, objective responses (ORs) were determined in 10% of cases (complete response—CR, and partial response—PR in 5% each). Progression-free survival (PFS) in ITT at six months was 17.5%. Overall survival (OS) was 28.3% at one year, 2.6% at two years, five and ten years. In the RGBM population, objective responses (ORs) were determined in 13.3% of cases (CR and PR in 6.7% each). PFS in RGBM at six months was 16.7%. OS was 34.7% at one year, 3.47% at two years, five?and ten years. In the ERGBM population, ORs were determined in 16.7% of cases (CR and PR in?8.3% each). PFS in ERGBM at six months was 20.8%, OS was 39.3% at one year, 4.4% at two years, five and ten years. The treatment was well-tolerated with reversible Grades 3 and 4 toxicity in 17.5% of patients (7 patients who experienced multiple toxicities) and no chronic toxicity. In conclusion, the study reached efficacy endpoint. ANP is well-tolerated and compares favorably to the current treatment for RGBM.
文摘Purpose: The main objective of the study was to evaluate the effect of air gaps of 0 - 5.0 cm between bolus and skin for 1.0 cm Superflab bolus on surface dose (DSurf) and depth of maximum dose (dmax) in solid water and Rando? phantoms. Methods: In this work, the effects of bolus to surface distance on DSurf and variation in dmax were analyzed in a solid water phantom and in an anthropomorphic Rando? phantom for different field sizes, using Gafchromic? EBT films and farmer chamber. Results: For field sizes of 5 × 5 cm2 the DSurf is significantly affected by increasing air gaps greater than 5 mm. For field sizes larger than 10 × 10 cm2, DSurf is nearly the same for air gaps of 0 - 5.0 cm. For small fields and 6 MV photon beam, dmax increases with increasing air gap, while for 10 MV beam and smaller field sizes (i.e. 5 × 5 and 10 × 10 cm2) the dmax first decreases and then increases with the air gaps. For both 3DCRT and IMRT plans on Rando?, DSurf reduction is more prominent with increasing air gaps. Conclusion: For field sizes larger than 10 × 10 cm2 DSurf is largely unaffected by air gaps. However, smaller air gap results in shallower dmax for both 6 MV and 10 MV photon beams at all fields sizes. Special consideration should be taken to reduce air gaps between bolus and skin for field sizes smaller than 10 × 10 cm2 or when surface contour variations are greater or when the bolus covers small area and at the border of the field.
文摘Squamous cell carcinoma accounts for 90% of all oral cancers. It may affect any anatomical site in the mouth, but most commonly the tongue and the floor of the mouth. It usually arises from a pre-existing potentially malignant lesion, and occasionally de novo;but in either case from within a field of precancerized epithelium. The use of tobacco and betel quid, heavy drinking of alcoholic beverages and a diet low in fresh fruits and vegetables are well known risk factors for oral squamous cell carcinoma. Important risk factors related to the carcinoma itself that are associated with a poor prognosis include large size of the tumour at the time of diagnosis, the presence of metastases in regional lymphnodes, and a deep invasive front of the tumour. Squamous cell carcinoma is managed by surgery, radiation, and chemotherapy singularly or in combination;but regardless of the treatment modality, the five-year survival rate is poor at about 50%. This can be attributed to the fact that about two-thirds of persons with oral squamous cell carcinoma already have a large lesion at the time of diagnosis.
文摘Background: Since advanced hepatocellular carcinoma (HCC) is potentially fatal, and patients’ quality of life (QOL) often deteriorates during their treatment, improving the prognosis and QOL of patients given chemotherapy is very important. In addition, cost-effective treatments are highly desirable when chemotherapy must be given repeatedly. The aim of this study was to evaluate the efficacy and usefulness of 5-fluorouracil (5-FU) and high-concentration cisplatin by short-term hepatic arterial infusion chemotherapy (3-day FPL) in advanced HCC patients. Methods: Thirty patients with unresectable advanced HCC were enrolled. The patients underwent hepatic arterial infusion chemotherapy via the implanted port system with 5-FU on days 1 - 3 and a fine-powder formulation of cisplatin in suspended pre-warmed lipiodol on day 2 every 4 to 10 weeks. Tumor response was assessed one month later with CT. Results: All patients had evidence of portal vein invasion (Vp2-4). Four patients achieved a complete response (CR), 8 patients achieved a partial response (PR), and 7 patients had stable disease (SD). The median progression-free survival (PFS) and overall survival (OS) were 198 days and 452 days, respectively. The OS was significantly longer in the successful disease control group (CR, PR, and SD) than in the progressive disease group (P < 0.005). Conclusions: Three-day FPL was effective and tolerable in advanced HCC patients due to its shorter time of administration than conventional FP therapy. Therefore, repetitive 3-day FPL appears useful and contributes to improving the prognosis and QOL of patients with advanced HCC. In addition, this protocol is a cost-effective treatment.
文摘Cordycepin is an active component of parasitic fungus, Cordyceps militaris, and investigated for its pharmacologic efficacy. Increasing evidence supports the anti-tumoral effects of Cordycepin in various types of human solid tumors. We sought to determine the effects of Cordycepin on oral squamous cell carcinoma in vitro and in vivo. Two oral squamous cell carcinoma cell lines, KB and HSC3, were used in this study. Cells were treated with Cordycepin or diluent, followed by determinations of proliferation by sulforhodamine method and apoptosis by TUNEL assay in vitro. For in vivo experiments, tumor cells were transplanted into nude mice, followed by treatment with Cordycepin or control diluent. In addition, cells were examined for expression of adenosine receptor isotypes, and tested whether cordycepin-induced effects were mediated through adenosine receptors by combinatorial treatment of cordycepin and antagonists specific to each isotype of adenosine receptors. Two cell lines expressed protein of all types of adenosine receptors stronger than normal oral keratinocytes. Cordycepin showed anti-proliferating effect and apoptotic effect on both cell lines in vitro in a dose dependent manner. However, any adenosine receptors did not reverse the effect of cordycepin. In our in vivo experiments, cordycepin failed to decrease the tumor volume significantly, and failed to induce more apoptosis of tumor cells. Cordycepin has anti-proliferating effect and induces apoptosis not mediated by adenosine receptor on oral squamous cell carcinoma cells in vitro. However, in vivo results suggest that cordycepin in itself has a limited value as a novel chemotherapeutic agent for oral squamous cell carcinoma.
文摘Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies are needed for patients whose tumor recurs after first-line treatment. This single-arm, two-stage, interventional Phase II study evaluated the efficacy and safety of a combination of antineoplastons A10 and AS2-1. Nineteen patients were enrolled in the study (safety population), but fifteen patients with a median age of 9.4 years who met eligibility criteria were evaluated. The majority of subjects (12/15) were Caucasian and 8/15 (53%) were female. More than half (53%) of patients were diagnosed with glioblastoma and 33% with anaplastic astrocytoma. All patients had failed standard therapy including surgery, radiation, and chemotherapy. Antineoplastons were administered intravenously every four hours (median dose of A10 6.9 g/kg/d and AS2-1 0.30 g/kg/d) until objective response was documented and thereafter for a further 8 months. Clinical evaluations were performed every 8 weeks. All patients enrolled in the study were included in the safety analysis but only patients fulfilling the inclusion criteria were included in the efficacy evaluation. The duration of treatment with antineoplastons ranged from 2 weeks to 120 weeks. A complete response was documented in 2/15 (13%), partial response in 2/15 (13%), stable disease in 3/15 (20%). Progression-free survival at six months was 47% and overall survival (OS) at one year was 33.3%. One patient (6.7%) survived 10 years from treatment start. A small group of patients suffered reversible Grade 3 and 4 toxicities including hypernatremia 2/19 (11%) and decrease of neutrophils 1/19 (5%). There were no chronic toxicities. There was improvement of quality of life in patients who had objective response. It is concluded that antineoplastons show efficacy with an acceptable profile in this cohort of patients with recurrent high-grade glioma.
文摘The present comparative review discusses conservation of early evolutionary, relic genetics in the genome of man, which determine two different mechanistic reductive division systems expressed by normal, human diploid cells. The divisions were orderly and segregated genomes reductively to near-diploid daughter cells, which showed gain of a proliferative advantage (GPA) over cells of origin. This fact of GPA expression is a fundamental requirement for initiation of tumorigenesis. The division systems were responses to a carcinogen-free induction system, consisting of short (1 - 3 days) exposures of young cells to nutritional deprivation of amino acid glutamine (AAD). In recovery growth (2 - 4 days) endo-tetra/ochtoploid cells and normal diploid metaphase cells demonstrated chromosomal reductive divisions to respectively heterozygous and homozygous altered daughter cells. Both division systems showed co-segregating whole complements, which for reduction of the diploid metaphases could only arise from gonomeric-based autonomous behavior of maternal and paternal (mat/pat) genomes. The timely associated appearance with these latter divisions was fast growing small-cells (1/2 volume-size reduced from normal diploidy), which became homozygous from haploid, genomic doubling. Both reductive divisions thus produced genome altered progeny cells with GPA, which was associated with pre-cancer-like cell-phenotypic changes. Since both “undesirable” reductive divisions expressed orderly division sequences, their genetic controls were assumed to be “old genetics”, evolutionarily conserved in the genome of man. Support for this idea was a search for evidential material in the evolutionary record from primeval time, when haploid organisms were established. The theory was that endopolyploid and gonomery-based reductive divisions relieved the early eukaryotic organisms from accidental, non-proliferative diploidy and polyploidy, bringing the organism back to vegetative haploid proliferation. Asexual cycles were common for maintenance of propagating haploid and diploid early unicellular eukaryotes. Reduction of accidental diploidy was referred to as “one-step meiosis” which meant gonomeric-based maternal and paternal genomic independent segregations. This interpretation was supported by exceptional chromosomal behaviors. However, multiple divisions expressing non-disjunction was the choice-explanation from evolutionists, which today is also suggested for the rarer LL-1 near haploid leukemia. These preserved non-mitotic mechanistic divisions systems are today witnessed in apomixes and parthenogenesis in many animal phyla. Thus, the indications are the modern genome of man harbors, relic-genetics from past “good” evolvements assuring “stable” proliferation of ancient, primitive eukaryotes, but with cancer-like effects for normal human cells.
文摘Antineoplastons are peptide and amino acid derivatives that occur naturally in the human body. They inhibit the growth of neoplastic cells without growth inhibition of normal cells. Phenylacetylglutaminate (PG) is an active ingredient of antineoplastons A10 and AS2-1 (ANP) and is also a metabolic by-product of phenylbutyrate (PB). The formulation of antineoplaston AS2-1 is a 4:1 mixture of phenylacetate (PN) and PG. Antineoplaston A10 is a 4:1 mixture of PG and isoPG. This study investigates the molecular mechanism of action of PG and PN. The Human U87 glioblastoma (GBM) cell line was used as the model system in this study. A total human gene array screen using the Affymetrix Human Genome plus 2.0 oligonucleotide arrays was performed using mRNA derived from U87 cells exposed to PG and PN. Pathway analysis was performed to allow the visualization of effect on metabolic pathways and gene interaction networks. Our preliminary results indicate that PG and PN interrupt signal transduction in RAS/MAPK/ERK and PI3K/AKT/PTEN pathways, interfere with cell cycle, decrease metabolism and promote apoptosis in human U87 GBM cells. The effect on multiple cellular pathways and targets, suggests that ANP and PB are promising candidates for clinical studies in GBM.
文摘Introduction: Systematic lymphadenectomy and ligation of the feeding artery is extremely important when performing radical resection in colorectal cancer. However, vascular surgery via laparoscopy requires advanced skills and techniques;thus, this procedure needs to be simplified while maintaining quality of the surgery to make it a preferred technique for the surgeons. Methods: There were 49 patients who underwent laparoscopic sigmoidectomy or anterior resection till T2 level for sigmoid colon cancer and recto-sigmoid colon cancer. We analyzed short-term and long-term outcomes between stapling ligation and clipping ligation techniques used in these surgeries. Results: The mean volume of blood loss in the stapling ligation group was 12.8 ± 12.3 ml, which was significantly lower than 41.9 ± 71.2 ml of mean volume of blood loss in the clipping ligation group. There was no significant difference in the mean duration of surgery, the mean number of harvested lymph nodes, morbidity, recurrence, and 5-year relapse free survival rates between the 2 groups. Conclusions: This study demonstrates a surgical technique using staplers for vascular treatment of tumor-feeding arteries as a new technical improvement in laparoscopic colectomy for the treatment of early-stage colon cancer. We found that the described procedure was technically safe, simple, convenient, and oncologically valid.
文摘Colorectal cancer (CRC) is the second leading cause of cancer death related mortality with 1.2 million new cases diagnosed annually worldwide. Despite remarkable advances in the treatment of resectable CRC, advanced disease that recurs following initial two lines of chemotherapy, remains incurable. Targeted therapies using a single agent or in combination with other drugs have been tested in a number of clinical trials, with only moderate improvement. Here we present preliminary findings of improved overall survival (OS) using a combination of sodium phenylbutyrate with various targeted and chemotherapeutic agents in stage IV CRC patients who had failed at least two lines of chemotherapy. Results suggest a strategy of simultaneous interruption of signal transduction involving EGFR (VEGF)?KRAS-ERK and PI3K-AKT pathways and interference with cell cycle, cancer cell metabolism, maintenance of cancerous stem cells, and promotion of apoptosis. In a group of 15 patients, median OS was higher compared to other third-line therapies (14.7 months compared to between 4.8 and 9.5 months in other studies). Given the understanding that our findings are preliminary, we propose the validation of our initial results using a well-designed phase I/II trial in recurrent advanced colorectal cancer.
