C Goswami

Publications of C Goswami

• TRPV1 expression-dependent initiation and regulation of filopodia.

  Authors: C Goswami, T Hucho

  Journal of neurochemistry. 12/2007; 103(4):1319-33.

  Transient receptor potential vanilloid subtype 1 (TRPV1), a non-selective cation channel, is present endogenously in dorsal root ganglia (DRG) neurons. It is involved in the recognition of variousTransient receptor potential vanilloid subtype 1 (TRPV1), a non-selective cation channel, is present endogenously in dorsal root ganglia (DRG) neurons. It is involved in the recognition of various pain producing physical and chemical stimuli. In this work, we demonstrate that expression of TRPV1 induces neurite-like structures and filopodia and that the expressed protein is localized at the filopodial tips. Exogenous expression of TRPV1 induces filopodia both in DRG neuron-derived F11 cells and in non-neuronal cells, such as HeLa and human embryonic kidney (HEK) cells. We find that some of the TRPV1 expression-induced filopodia contain microtubules and microtubule-associated components, and establish cell-to-cell extensions. Using live cell microscopy, we demonstrate that the filopodia are responsive to TRPV1-specific ligands. But both, initiation and subsequent cell-to-cell extension formation, is independent of TRPV1 channel activity. The N-terminal intracellular domain of TRPV1 is sufficient for filopodial structure initiation while the C-terminal cytoplasmic domain is involved in the stabilization of microtubules within these structures. In addition, exogenous expression of TRPV1 results in altered cellular distribution and in enhanced endogenous expression of non-conventional myosin motors, namely myosin IIA and myosin IIIA. These data indicate a novel role of TRPV1 in the regulation of cellular morphology and cellular contact formation.

• Identification and characterisation of novel tubulin-binding motifs located within the C-terminus of TRPV1.

  Authors: C Goswami, Tim B Hucho, F Hucho

  Journal of neurochemistry. 05/2007; 101(1):250-62.

  Previously, we reported that TRPV1, the vanilloid receptor, interacts with soluble alphabeta-tubulin dimers as well as microtubules via its C-terminal cytoplasmic domain. The interacting region ofPreviously, we reported that TRPV1, the vanilloid receptor, interacts with soluble alphabeta-tubulin dimers as well as microtubules via its C-terminal cytoplasmic domain. The interacting region of TRPV1, however, has not been defined. We found that the TRPV1 C-terminus preferably interacts with beta-tubulin and less with alpha-tubulin. Using a systematic deletion approach and biotinylated-peptides we identified two tubulin-binding sites present in TRPV1. These two sequence stretches are highly conserved in all known mammalian TRPV1 orthologues and partially conserved in some of the TRPV1 homologues. As these sequence stretches are not similar to any known tubulin-binding sequences, we conclude that TRPV1 interacts with tubulin and microtubule through two novel tubulin-binding motifs.

• TRPV1 at nerve endings regulates growth cone morphology and movement through cytoskeleton reorganization.

  Authors: C Goswami, H Schmidt, F Hucho

  The FEBS journal. 03/2007; 274(3):760-72.

  While the importance of Ca(2+) channel activity in axonal path finding is established, the underlying mechanisms are not clear. Here, we show that transient receptor potential vanilloid receptor 1While the importance of Ca(2+) channel activity in axonal path finding is established, the underlying mechanisms are not clear. Here, we show that transient receptor potential vanilloid receptor 1 (TRPV1), a member of the TRP superfamily of nonspecific ion channels, is physically and functionally present at dynamic neuronal extensions, including growth cones. These nonselective cation channels sense exogenous ligands, such as resenifera toxin, and endogenous ligands, such as N-arachidonoyl-dopamine (NADA), and affect the integrity of microtubule cytoskeleton. Using TRPV1-transiently transfected F11 cells and embryonic dorsal root ganglia explants, we show that activation of TRPV1 results in growth cone retraction, and collapse and formation of varicosities along neurites. These changes were due to TRPV1-activation-mediated disassembly of microtubules and are partly Ca(2+)-independent. Prolonged activation with very low doses (1 nM) of NADA results in shortening of neurites in the majority of isolectin B4-positive dorsal root ganglia neurones. We postulate that TRPV1 activation plays an inhibitory role in sensory neuronal extension and motility by regulating the disassembly of microtubules. This might have a role in the chronification of pain.

• Rapid disassembly of dynamic microtubules upon activation of the capsaicin receptor TRPV1.

  Authors: C Goswami, M Dreger, H Otto, B Schwappach, F Hucho

  Journal of neurochemistry. 02/2006; 96(1):254-66.

  The transmission of pain signalling involves the cytoskeleton, but mechanistically this is poorly understood. We recently demonstrated that the capsaicin receptor TRPV1, a non-selective cationThe transmission of pain signalling involves the cytoskeleton, but mechanistically this is poorly understood. We recently demonstrated that the capsaicin receptor TRPV1, a non-selective cation channel expressed by nociceptors that is capable of detecting multiple pain-producing stimuli, directly interacts with the tubulin cytoskeleton. We hypothesized that the tubulin cytoskeleton is a downstream effector of TRPV1 activation. Here we show that activation of TRPV1 results in the rapid disassembly of microtubules, but not of the actin or neurofilament cytoskeletons. TRPV1 activation mainly affects dynamic microtubules that contain tyrosinated tubulins, whereas stable microtubules are apparently unaffected. The C-terminal fragment of TRPV1 exerts a stabilizing effect on microtubules when over-expressed in F11 cells. These findings suggest that TRPV1 activation may contribute to cytoskeleton remodelling and so influence nociception.

• Identification and characterization of a Ca2+ -sensitive interaction of the vanilloid receptor TRPV1 with tubulin.

  Authors: C Goswami, M Dreger, R Jahnel, O Bogen, C Gillen, F Hucho

  Journal of neurochemistry. 01/2005; 91(5):1092-103.

  The vanilloid receptor TRPV1 plays a well-established functional role in the detection of a range of chemical and thermal noxious stimuli, such as those associated with tissue inflammation and theThe vanilloid receptor TRPV1 plays a well-established functional role in the detection of a range of chemical and thermal noxious stimuli, such as those associated with tissue inflammation and the resulting pain. TRPV1 activation results in membrane depolarization, but may also trigger intracellular Ca2+ -signalling events. In a proteomic screen for proteins associated with the C-terminal sequence of TRPV1, we identified beta-tubulin as a specific TRPV1-interacting protein. We demonstrate that the TRPV1 C-terminal tail is capable of binding tubulin dimers, as well as of binding polymerized microtubules. The interaction is Ca2+ -sensitive, and affects microtubule properties, such as microtubule sensitivity towards low temperatures and nocodazole. Our data thus provide compelling evidence for the interaction of TRPV1 with the cytoskeleton. The Ca2+ -sensitivity of this interaction suggests that the microtubule cytoskeleton at the cell membrane may be a downstream effector of TRPV1 activation.

• Hodgkin's disease relapse presenting as Pancoast's syndrome.

  Authors: C Goswami, K A Dinshaw, S K Shrivastava, M A Muckaden, V Sharma, S H Advani

  Indian journal of cancer. 04/1996; 33(1):21-3.

  Among the various infrequent causes of Pancoast's syndrome, Hodgkin's disease is one. A 26 year old man was diagnosed as Hodgkin's disease. Five years later the disease relapsed producing Pancoast'sAmong the various infrequent causes of Pancoast's syndrome, Hodgkin's disease is one. A 26 year old man was diagnosed as Hodgkin's disease. Five years later the disease relapsed producing Pancoast's syndrome. The importance of precise aetiological diagnosis before treatment of such cases with similar presentation is emphasized.

• Hodgkin′s disease relapse presenting as Pancoast′s syndrome.

  Authors: C Goswami, K Dinshaw, S Shrivastava, M Muckaden, V Sharma, S Advani

  Indian Journal of Cancer. 01/1996;

  Among the various infrequent causes of Pancoast′s syndrome, Hodgkin′s disease is one. A 26 year old man was diagnosed as Hodgkin′s disease. Five years later the disease relapsed producing Pancoast′sAmong the various infrequent causes of Pancoast′s syndrome, Hodgkin′s disease is one. A 26 year old man was diagnosed as Hodgkin′s disease. Five years later the disease relapsed producing Pancoast′s syndrome. The importance of precise aetiological diagnosis before treatment of such cases with similar presentation is emphasized.

• Management of primary and metastatic triple negative breast cancer: perceptions of oncologists from India.

  Authors: P M Parikh, S Gupta, B Parikh, B K Smruti, J Issrani, S Topiwala, C Goswami, G S Bhattacharya, T Sen, J S Sekhon, H Malhotra, S Nag, R T Chacko, K Babu Govind, T Raja, A K Vaid, D C Doval, P K Das

  Indian journal of cancer. 48(2):158-64.

  In order to document the understanding of current evidence for the management of triple negative breast cancer and application of this knowledge in daily practice, we conducted an interactive surveyIn order to document the understanding of current evidence for the management of triple negative breast cancer and application of this knowledge in daily practice, we conducted an interactive survey of practicing Indian oncologists. A core group of academic oncologists devised two hypothetical triple negative cases (metastatic and early breast cancer, respectively) and multiple choice options under different clinical circumstances. The respondents were practicing oncologists in different Indian cities who participated in either an online survey or a meeting. The participants electronically chose their preferred option based on their everyday practice. A total of 152 oncologists participated. Just over half (53.8%) preferred taxane based chemotherapy as first-line chemotherapy in the metastatic setting. In the adjuvant setting, a taxane regimen was chosen by 61%. Over half of respondents (52.6%) underestimated the baseline survival of a patient with node positive triple-negative tumor and 18.9% overestimated this survival compared to the estimate of the Adjuvant! program. This data offers insight into the perceptions and practice of a diverse cross-section of practicing oncologists in India with respect to their therapeutic choices in metastatic and adjuvant settings in triple negative breast cancer.

• Cetuximab plus radiotherapy in patients with unresectable locally advanced squamous cell carcinoma of head and neck region--a open labelled single arm phase II study.

  Authors: S Dattatreya, C Goswami

  Indian journal of cancer. 48(2):154-7.

  To evaluate feasibility, safety and outcome of cetuximab concurrent with radiotherapy in locally advanced head-neck cancer. Between March 2007 and January 2008 eligible cases of locally advancedTo evaluate feasibility, safety and outcome of cetuximab concurrent with radiotherapy in locally advanced head-neck cancer. Between March 2007 and January 2008 eligible cases of locally advanced unresectable (Stage IV) squamous cell carcinoma of head and neck were enrolled in this single arm, open labeled phase II Study. They were treated with cetuximab for a duration of 8 weeks and concomitant RT for 7 weeks (starting one week after initiating Cetuximab). A total of 19 eligible patients were enrolled. The median age of patients was 53 years, all patients happening to be male. The performance status of the patients was 0/1. The location of the primary tumor was oropharynx in 12 cases, oral cavity in 4, larynx in 2, and hypopharynx in one case. The overall response rate (ORR) was 68.42% and the overall survival at 2 year was 84 %. All 13 patients who completed two years follow-up after completion of study treatment continued to be alive with no evidence of disease progression. One patient also remained alive with progressive disease. Cetuximab concurrent with radiotherapy is a safe and effective option in advanced head-neck cancer patients.