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Ultrasonics Sonochemistry Sep 2017Interest in mechanical high intensity focused ultrasound (HIFU) ablation is rapidly growing. Boiling histotripsy (BH) is applied for mechanical fragmentation of soft...
Interest in mechanical high intensity focused ultrasound (HIFU) ablation is rapidly growing. Boiling histotripsy (BH) is applied for mechanical fragmentation of soft tissue into submicron fragments with limited temperature increase using the shock wave and cavitation effects of HIFU. Research on BH has been largely limited to ex vivo experiments. As a consequence, the in vivo pathology after BH treatment and the relation to preexistent tissue characteristics are not well understood. This study reports on in vivo MR guided BH treatment, either with 100 or 200 pulses per focal spot, in three different subcutaneous mouse tumor models: a soft-tissue melanoma (B16OVA), a compact growing thymoma (EL4), and a highly vascularized neuroblastoma (9464D). Extensive treatment evaluation was performed using MR imaging followed by histopathology 2h after treatment. T2 weighted MRI allowed direct in vivo visualization of the BH lesions in all tumor models. The 100-pulse treated area in the B16OVA tumors was larger than the predicted treatment volume (500±10%). For the more compact growing EL4 and 9464D tumors this was 95±13% and 55±33%, respectively. Histopathology after the 100-pulse treatment revealed completely disintegrated lesions in the treated area with sharp borders in the compact EL4 and 9464D tumors, while for B16OVA tumors the lesion contained a mixture of discohesive (partly viable) clusters of cells, micro-vessel remainings, and tumor cell debris. The treatment of B16OVA with 200 pulses increased the fragmentation of tumor tissue. In all tumor types only micro-hemorrhages were detected after ablation (slightly higher after 200-pulse treatment for the highly vascularized 9464D tumors). Collagen staining revealed that the collagen fibers were to a greater or lesser extent still intact and partly clotted together near the lesion border in all tumor models. In conclusion, this study reveals effective mechanical fragmentation of different tumor types using BH without major hemorrhages. However, treatment settings may need to be adjusted to the tissue characteristics for optimal tissue fragmentation.
Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Female; High-Intensity Focused Ultrasound Ablation; Magnetic Resonance Imaging; Mice; Surgery, Computer-Assisted; Thymoma; Thymus Neoplasms
PubMed: 28633808
DOI: 10.1016/j.ultsonch.2017.02.035 -
Scientific Reports Feb 2020The development of personalized therapies represents an urgent need owing to the high rate of cancer recurrence and systemic toxicity of conventional drugs. So far,...
The development of personalized therapies represents an urgent need owing to the high rate of cancer recurrence and systemic toxicity of conventional drugs. So far, targeted toxins have shown promising results as potential therapeutic compounds. Specifically, toxins conjugated to antibodies or fused to growth factors/enzymes have been largely demonstrated to selectively address and kill cancer cells. We investigated the anti-tumor potential of a chimeric recombinant fusion protein formed by the Ribosome Inactivating Protein saporin (SAP) and the amino-terminal fragment (ATF) of the urokinase-type plasminogen activator (uPA), whose receptor has been shown to be over-expressed on the surface of aggressive tumors. ATF-SAP was recombinantly produced by the P. pastoris yeast and its activity was assessed on a panel of bladder and breast cancer cell lines. ATF-SAP resulted to be highly active in vitro, as nano-molar concentrations were sufficient to impair viability on tumor cell lines. In contrast to untargeted toxins, the chimeric fusion protein displayed a significantly improved toxic effect in uPAR-expressing cells, demonstrating that the selective activity was due to the presence of the targeting moiety. Fibroblasts were not sensitive to ATF-SAP despite uPAR expression, indicating that cell-specific receptor-mediated internalization pathway(s) might be considered. The in vivo anti-tumor effect of the chimera was shown in a bladder cancer xenograft model. Current findings indicate ATF-SAP as a suitable anti-tumoral therapeutic option to cope with cancer aggressiveness, as a single treatment or in combination with traditional therapeutic approaches, to appropriately address the intra- and inter- tumor heterogeneity.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Female; Humans; Mice; Mice, Nude; Neoplasms; Receptors, Urokinase Plasminogen Activator; Recombinant Fusion Proteins; Saporins; Triple Negative Breast Neoplasms; Urinary Bladder Neoplasms; Urokinase-Type Plasminogen Activator
PubMed: 32054892
DOI: 10.1038/s41598-020-59313-8 -
BMC Surgery Aug 2022Stapled haemorrhoidopexy (SH) has resulted in a unique collection of procedural complications with postoperative mucocele a particularly rare example. This study is...
BACKGROUND
Stapled haemorrhoidopexy (SH) has resulted in a unique collection of procedural complications with postoperative mucocele a particularly rare example. This study is designed to comprehensively describe the characteristics of rectal mucocele and discuss its pathogenesis following SH surgery.
METHODS
A database of patients presenting with a rectal mucocele following an SH procedure was established and studied retrospectively.
RESULTS
Seven patients (5 males; median age 32 years, range 20-75 years) were identified. All patients complained of variable anal discomfort with 5/7 presenting with inconstant anal pain, 2 with de novo evacuatory difficulty. These cases appeared at a median time of 6 months (range 2-84 months) after SH surgery.
CONCLUSION
Rectal Mucocele develops when mucosal fragments become embedded and isolated under the mucosa. It is a preventable complication of SH surgery by ensuring correct purse string placement prior to stapled haemorrhoid excision.
Topics: Adult; Aged; Hemorrhoids; Humans; Male; Middle Aged; Mucocele; Postoperative Complications; Rectum; Retrospective Studies; Surgical Stapling; Treatment Outcome; Young Adult
PubMed: 35915446
DOI: 10.1186/s12893-022-01744-3 -
Japanese Journal of Cancer Research :... Aug 2000TZT-1027, a dolastatin 10 derivative, is an antimicrotubule agent with potent antitumor activity both in vitro and in vivo. In this study, we performed biochemical and...
TZT-1027, a dolastatin 10 derivative, is an antimicrotubule agent with potent antitumor activity both in vitro and in vivo. In this study, we performed biochemical and histopathological examinations, and evaluated TZT-1027-induced tumoral vascular collapse and tumor cell death in an advanced tumor model, murine colon 26 adenocarcinoma. In addition, we studied the effects of TZT-1027 on cultured human umbilical vein endothelial cells (HUVEC). Tolerable doses of TZT-1027 induced tumor-selective hemorrhage within 1 h. This hemorrhage occurred mainly in the peripheral area of the tumor mass. Measurements of tumoral hemoglobin content and dye permeation revealed that the hemorrhage occurred firstly and tumor blood flow stopped secondarily. The vascular damage was followed by continuous induction of apoptosis of the tumor cells, tumor tissue necrosis, and tumor regression. In cultured HUVEC, TZT-1027 induced marked cell contraction with membrane blebbing in 30 min. These cell changes were completely inhibited by K252a, a broad-spectrum inhibitor of protein kinases. These effects of TZT-1027 on both tumor vasculature and HUVEC were greater than those of vincristine. In conclusion, TZT-1027 quickly attacked the well-developed vascular system of advanced tumors by a putative protein kinase-dependent mechanism, and then blocked tumor blood flow. Therefore, TZT-1027 has both a conventional antitumor activity and a unique anti-tumoral vascular activity, making it a potentially powerful tool for clinical cancer therapy.
Topics: Animals; Antineoplastic Agents; Cell Survival; Colonic Neoplasms; DNA Fragmentation; Disease Models, Animal; Endothelium, Vascular; Female; Hemoglobins; Humans; Mice; Mice, Inbred BALB C; Microtubules; Neoplasm Transplantation; Neovascularization, Pathologic; Oligopeptides; Permeability; Tumor Cells, Cultured
PubMed: 10965026
DOI: 10.1111/j.1349-7006.2000.tb01022.x -
Cancer Control : Journal of the Moffitt... 2020Uniquely in nature, living systems must acquire, store, and act upon information. The survival and replicative fate of each normal cell in a multicellular organism is...
Uniquely in nature, living systems must acquire, store, and act upon information. The survival and replicative fate of each normal cell in a multicellular organism is determined solely by information obtained from its surrounding tissue. In contrast, cancer cells as single-cell eukaryotes live in a disrupted, heterogeneous environment with opportunities and hazards. Thus, cancer cells, unlike normal somatic cells, must constantly obtain information from their environment to ensure survival and proliferation. In this study, we build upon a simple mathematical modeling framework developed to predict (1) how information promotes population persistence in a highly heterogeneous environment and (2) how disruption of information resulting from habitat fragmentation increases the probability of population extinction. Because (1) tumors grow in a highly heterogeneous microenvironment and (2) many cancer therapies fragment tumors into isolated, small cancer cell populations, we identify parallels between these 2 systems and develop ideas for cancer cure based on lessons gleaned from Anthropocene extinctions. In many Anthropocene extinctions, such as that of the North American heath hen (), a large and widespread population was initially reduced and fragmented owing to overexploitation by humans (a "first strike"). After this, the small surviving populations are vulnerable to extinction from environmental or demographic stochastic disturbances (a "second strike"). Following this analogy, after a tumor is fragmented into small populations of isolated cancer cells by an initial therapy, additional treatment can be applied with the intent of extinction (cure). Disrupting a cancer cell's ability to acquire and use information in a heterogeneous environment may be an important tactic for causing extinction following an effective initial therapy. Thus, information, from the scale of cells within tumors to that of species within ecosystems, can be used to identify vulnerabilities to extinction and opportunities for novel treatment strategies.
Topics: Cytoskeleton; Ecosystem; Humans; Integrins; Models, Theoretical; Neoplasms; Tumor Microenvironment
PubMed: 32762341
DOI: 10.1177/1073274820945980 -
Journal of Ovarian Research Mar 2021Limited studies have reported the relationship between intestinal flora dysbiosis and clinical characteristics in polycystic ovary syndrome (PCOS). However, the...
BACKGROUND
Limited studies have reported the relationship between intestinal flora dysbiosis and clinical characteristics in polycystic ovary syndrome (PCOS). However, the structure and characteristics of gut microbiota in PCOS have not been fully elucidated.
OBJECTIVE
To analyze the composition of the Intestinal flora population in normal-weight women with PCOS and insulin resistance(IR) compared to PCOS alone and healthy women.
METHODS
A total of 14 PCOS patients with insulin resistant(PCOS-IR) and 12 PCOS alone (PCOS-NIR), and 10 age- and body mass index-matched healthy control women (HC). BMI: 18.5-23.9 kg/m. The bacterial 16 S rDNA V3-V4 fragment was amplified and sequenced. Then, the sequencing data were analyzed for species annotation, community diversity, and inter-group differences, to explore gut microbial characteristics of the subjects and their correlation with clinical parameters.
RESULTS
No significant difference in diversity was observed between PCOA and sample cluster analysis among the three groups (Beta-diversity) and Alpha-diversity. The relative abundance of Rothia, Ruminococcus, and Enterococcus was significantly higher in the PCOS-IR group than in the other two groups (P < 0.05), while that of Prevotella was dramatically decreased (P < 0.05). The abundance of Enterococcus was positively correlated with waist circumference, hip circumference, diastolic blood pressure, and insulin resistance index. Meanwhile, Rothia abundance is positively associated with waist circumference and free fatty acids.
CONCLUSIONS
The gut microbial composition of PCOS patients with insulin resistance is different from that of PCOS alone and healthy women. The difference is correlated with the clinical characteristics of PCOS, with regards to insulin resistance, abdominal obesity, free fatty acids, and other indicators. PCOS-IR patients have an increased abundance of Enterococcus which potentially the intestinal environment of the host by enriching the metabolic pathways related to insulin resistance, causing the occurrence and development of PCOS.
Topics: Adult; Female; Gastrointestinal Microbiome; High-Throughput Nucleotide Sequencing; Humans; Insulin Resistance; Polycystic Ovary Syndrome
PubMed: 33773586
DOI: 10.1186/s13048-021-00799-9 -
The Turkish Journal of Gastroenterology... Sep 2021Gastric cancer (GC) is a common cause of cancer-related deaths. The poor clinical outcome in GC patients is partially associated with a lack of appropriate diagnostic...
BACKGROUND
Gastric cancer (GC) is a common cause of cancer-related deaths. The poor clinical outcome in GC patients is partially associated with a lack of appropriate diagnostic and prognostic biomarkers. In the present study, we evaluated the diagnostic and prognostic values of cell-free DNA (cfDNA) integrity and the concentration of circulating nucleosomes (cNUCs).
METHODS
In the study, 40 GC patients and 55 GC-free individuals were enrolled. Cell-free DNA integrity was calculated as the ratio of concentration of the longer ACTB (beta-actin) gene fragment to that of the shorter ACTB fragment, measured using quantitative PCR. Circulating nucleosomes were measured by an ELISA-based approach.
RESULTS
We found that cfDNA integrity is higher in GC patients than in the control subjects (relative median values 0.51 vs. 0.38, respectively, P = .56) indicating prominent abundance of longer fragments in the patients. The patients with larger tumors (T3-4) had significantly higher cfDNA integrity than those with T1-T2 tumors. We also found GC patients to have higher concentrations of cNUCs in their plasma (relative median values 3.64 vs. 3.1). Importantly, the patients with high cfDNA integrity (i.e., lower fragmentation) had longer overall survival rates at 3 years than those with lower cfDNA integrity (76.5% vs. 38.9%, P = .02).
CONCLUSION
Cell-free DNA fragmentation has a prognostic value. However, it has no diagnostic value in GC.
Topics: Biomarkers, Tumor; Cell-Free Nucleic Acids; Humans; Prognosis; Stomach Neoplasms
PubMed: 34609300
DOI: 10.5152/tjg.2021.20832 -
Diagnostic Pathology May 2017HER2 assessment in biopsy specimens of gastric cancer (GC) is challenging because of the intratumoral heterogeneity. False negative results may be get because of limited...
BACKGROUND
HER2 assessment in biopsy specimens of gastric cancer (GC) is challenging because of the intratumoral heterogeneity. False negative results may be get because of limited biopsy material. The aim of this study is to explore how tumor-containing fragment number and biopsy specimen number affect HER2 immunohistochemistry (IHC) positive rate.
METHODS
Eight hundred and ninety biopsy specimens and 459 paired resected specimens were collected. IHC staining of HER2 was performed. HER2 IHC positive (scored 3+) rate was compared based on tumor-containing fragment number, biopsy specimen number, average size and tumor tissue proportion of tumor-containing fragments. The positive predictability of biopsy specimens to resected specimens was analyzed based on tumor fragment number.
RESULTS
HER2 IHC positive rates were 2.0, 3.5, 7.0, 13.2, 17.1, and 15.9% when tumor fragment numbers were 1, 2, 3, 4, 5 and 6 respectively. The rate rose with the increase of tumor fragment number (P = 0.004). ROC curve analysis showed that biopsy specimens exhibited positive predictability when tumor fragment number reached 3, but showed better performance when the number was ≥4 (P < 0.05). After fragment number reached 4, no statistic differences were reached in either HER2 IHC positive rate or positive predictability with further increase of the number (P > 0.05). HER2 IHC positive rate was not associated with biopsy number (P = 0.127), average size of tumor fragments (P = 0.397), and tumor tissue proportion of tumor fragments (P = 0.825) directly.
CONCLUSIONS
The number of tumor-containing fragments influences HER2 IHC positive (scored 3+) rate. Greater than or equal to 4 (≥4) tumor fragments give better results in the positive rate as well as positive predictability. We recommend the number of tumor containing fragments be described in the HER2 IHC pathology reports for clinical reference in endoscopic biopsy specimens of GC.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers, Tumor; Biopsy; Female; Humans; Immunohistochemistry; Male; Middle Aged; Predictive Value of Tests; ROC Curve; Receptor, ErbB-2; Reproducibility of Results; Stomach Neoplasms; Young Adult
PubMed: 28549444
DOI: 10.1186/s13000-017-0616-5 -
The Neuroradiology Journal Feb 2023Neurocysticercosis, the commonest neuro-parasite, sometimes presents as complex ring enhancing lesion causing diagnostic dilemma. We aim to establish...
OBJECTIVES
Neurocysticercosis, the commonest neuro-parasite, sometimes presents as complex ring enhancing lesion causing diagnostic dilemma. We aim to establish radio-histo-morphological equivalents of early events in degeneration of the parasite to explain such imaging phenotypes.
METHODS
We compared patterns of degeneration in 23 randomly selected complex NCC on MRI with histo-morphology in 30 cysts obtained from an unrelated post mortem brain.
RESULTS
The anatomy of the parasite and the degenerative patterns of the scolex (hydropic changes, calcification, evagination, and fragmentation) and the cyst wall (undulation, accessory loculi, and frank disruption) were well demonstrated on both. The intact scolex remarkably resembled head of intestinal Taenia. The complex lesions were conglomeration of multiple communicating cysts with a single parent cyst and multiple daughter cysts. The parent cysts contained a solitary variably degenerated scolex, had thicker walls and associated chronic inflammation. The remaining cysts of the lesion complex contained no scolex, had poorly organized walls, turbid contents, and florid perilesional enhancement with leakage of contrast. Three lesions assumed a multi-cystic pseudo-tumorous pattern, of which two resolved into solitary calcific remnants on follow up.
CONCLUSION
Complex lesion in NCC result from degeneration of solitary parasite with perilesional gliosis, surrounded by multiple non-larval daughter cysts inciting acute intra and perilesional inflammation due to enhanced antigenic challenge. Possibly, attempted abortive asexual reproduction by the cellulose cyst as a preterminal event results in a "limited Racemose like transition." Correct interpretation has diagnostic and therapeutic implications as active lesions and their fibrocalcific residue may have greater epileptogenic potential.
Topics: Humans; Neurocysticercosis; Brain; Magnetic Resonance Imaging; Inflammation; Cysts
PubMed: 35538605
DOI: 10.1177/19714009221098372 -
Parasites & Vectors Oct 2022There are close similarities between the life-cycles of Echinococcus granulosus sensu lato (E. granulosus s.l.) that causes cystic echinococcosis (CE) in humans and...
BACKGROUND
There are close similarities between the life-cycles of Echinococcus granulosus sensu lato (E. granulosus s.l.) that causes cystic echinococcosis (CE) in humans and Taenia multiceps/Coenurus cerebralis that causes cerebral coenurosis in small ruminants. Recent evidence highlights that livestock in Maasai communities of northern Tanzania are suffering from increases in the prevalence of cerebral coenurosis, leading to concerns about a possible concurrent increased risk of human CE. The aim of this study was to estimate the prevalence of human abdominal CE and the prevalence and species/genotypes of E. granulosus s.l. in livestock in Maasai communities.
METHODS
Human CE was diagnosed by abdominal ultrasound on volunteers aged ≥ 7 years in five villages in the Longido and Ngorongoro Districts in northern Tanzania. Infection in ruminants was evaluated through inspection in local abattoirs, followed by molecular identification of one cyst per animal, with a priority for hepatic cysts, using PCR targeting of the cytochrome c oxidase I gene (COX1), followed by restriction fragment length polymorphism and multiplex PCR, and sequencing of non-E. granulosus s.l. samples.
RESULTS
Ultrasound was performed on 823 volunteers (n = 352 in two villages in Longido District, and n = 471 in three villages of Ngorongoro). Hepatic CE cases were diagnosed only in Ngorongoro (n = 6; 1.3%), of which three had active cysts. Village-level prevalence of CE ranged between 0 and 2.4%. Of the 697 ruminants inspected, 34.4% had parasitic cysts. Molecular identification was achieved for 140 of the 219 (63.9%) cysts sampled. E. granulosus s.l. and T. hydatigena/Cysticercus tenuicollis were identified in 51.4% and 48.6%, respectively, of livestock cysts. E. granulosus s.l. was identified in livestock from both Longido (35.3% of 116 genotyped cysts) and Ngorongoro (91.2% of 34 genotyped cysts). Of the total of 72 E. granuslosus s.l. cysts identified in livestock, 87.5% were E. granulosus sensu stricto (G1-G3 genotypes), 9.7% were E. ortleppi (G5) and one cyst was E. canadensis (G6-10). The three active human cysts, which were removed surgically, were G1-G3 genotypes.
CONCLUSIONS
Multiple species/genotypes of E. granulosus s.l. are circulating in Maasai communities of northern Tanzania. Human CE was detected in villages of Ngorongoro District and a high prevalence of echinococcal cysts was observed in livestock in both districts. More precise estimation of the prevalence in this area and a better understanding of the specific risk factors for CE among Maasai communities in northern Tanzania is needed. Interventions targeting transmission routes common to both E. granulosus s.l. and T. multiceps would have dual benefits for preventing both human and livestock disease.
Topics: Animals; Humans; Livestock; Pilot Projects; Neurocysticercosis; Tanzania; Echinococcosis; Echinococcus granulosus; Genotype; Cysts
PubMed: 36307877
DOI: 10.1186/s13071-022-05518-x